Difference between revisions of "Multiple myeloma, consolidation and maintenance"
Warner-admin (talk | contribs) m (Text replacement - "==TD {" to "==Thalidomide & Dexamethasone (TD) {") |
Warner-admin (talk | contribs) m (Text replacement - "'''contains dosing details in abstract'''" to "'''dosing details in abstract have been reviewed by our editors'''") |
||
(228 intermediate revisions by 5 users not shown) | |||
Line 1: | Line 1: | ||
− | + | <span id="BackToTop"></span> | |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|pcd}} | |
− | |||
− | |} | ||
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Multiple_myeloma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''. | ''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Multiple_myeloma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''. | ||
− | <br | + | <br>'''Note: due to its size/complexity, multiple myeloma has been split into sub-pages:''' |
*[[Multiple_myeloma,_induction|Induction (transplant eligible and ineligible)]] | *[[Multiple_myeloma,_induction|Induction (transplant eligible and ineligible)]] | ||
*First-line consolidation and maintenance [''this page''] | *First-line consolidation and maintenance [''this page''] | ||
*[[Multiple_myeloma,_relapsed-refractory|Relapsed/refractory, including subsequent consolidation and maintenance]] | *[[Multiple_myeloma,_relapsed-refractory|Relapsed/refractory, including subsequent consolidation and maintenance]] | ||
*[[Smoldering multiple myeloma]] | *[[Smoldering multiple myeloma]] | ||
− | + | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
Line 23: | Line 21: | ||
=Consolidation after first-line therapy= | =Consolidation after first-line therapy= | ||
''Note that there is no crisp distinction between consolidation and maintenance. Generally regimens that are intended for a long or indefinite duration would be considered maintenance, whereas regimens with a short intended course would be considered consolidation.'' | ''Note that there is no crisp distinction between consolidation and maintenance. Generally regimens that are intended for a long or indefinite duration would be considered maintenance, whereas regimens with a short intended course would be considered consolidation.'' | ||
− | |||
==Bortezomib monotherapy {{#subobject:dd778e|Regimen=1}}== | ==Bortezomib monotherapy {{#subobject:dd778e|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen variant #1 {{#subobject:66855e|Variant=1}}=== | ===Regimen variant #1 {{#subobject:66855e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 40: | Line 33: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674665/ Mellqvist et al. 2013 (NMSG 15/05)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674665/ Mellqvist et al. 2013 (NMSG 15/05)] | ||
|2005-2009 | |2005-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
− | |style="background-color:#d9ef8b"|Might have superior PFS | + | |style="background-color:#d9ef8b"|Might have superior PFS (primary endpoint) |
|- | |- | ||
|} | |} | ||
''This trial only included bortezomib-naive patients; induction regimen was not specified but the majority received Cy-Dex.'' | ''This trial only included bortezomib-naive patients; induction regimen was not specified but the majority received Cy-Dex.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *All patients underwent autologous hematopoietic cell transplant at least 3 months prior to starting consolidation. | + | *All patients underwent [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|autologous hematopoietic cell transplant]] consolidation at least 3 months prior to starting bortezomib consolidation. |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] as follows: | *[[Bortezomib (Velcade)]] as follows: | ||
− | **Cycles 1 & 2: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | + | **Cycles 1 & 2: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 |
− | **Cycles 3 to 6: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | + | **Cycles 3 to 6: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[:Category:Bisphosphonates|Bisphosphonates]] were administered "according to national guidelines." | *[[:Category:Bisphosphonates|Bisphosphonates]] were administered "according to national guidelines." | ||
− | + | '''21-day cycle for 2 cycles, then 28-day cycle for 4 cycles''' | |
− | '''22- | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen variant # | + | ===Regimen variant #2, 4 out of 5 weeks for 20 weeks {{#subobject:9a4fhg|Variant=1}}=== |
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1038/leu.2017.83 Einsele et al. 2017 (MMY-3012)] | ||
+ | |2006-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup><br>Median PFS: 33.6 vs 27.8 mo<br>(HR 0.75, 95% CI 0.59-0.97) | ||
+ | |- | ||
+ | |[https://doi.org/10.1038/leu.2017.83 Einsele et al. 2017 (MMY-3013)] | ||
+ | |2006-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup><br>Median PFS: 33.6 vs 27.8 mo<br>(HR 0.75, 95% CI 0.59-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the combined analysis.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
+ | '''35-day cycle for 4 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 4 out of 5 weeks for 25 weeks {{#subobject:9a4ece|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2014.58.7618 Niesvizky et al. 2015 (UPFRONT)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2007-2010 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3b RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#Bortezomib_.26_Dexamethasone_. | + | *Induction [[Multiple_myeloma,_induction#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]] x 8 versus [[Multiple_myeloma,_induction#VMP|VMP]] x 8 versus [[Multiple_myeloma,_induction#VTD|VTD]] x 8 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
− | |||
'''35-day cycle for 5 cycles''' | '''35-day cycle for 5 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #4, 4 out of 6 weeks for 24 weeks {{#subobject:e72a4c|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-11-395749 Kumar et al. 2012 (EVOLUTION)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2008-2009 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 2 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VDC|VDC]] versus [[Multiple_myeloma,_induction#VDC|VDC-mod]] versus [[Multiple_myeloma,_induction#RVD|VDR]] versus [[Multiple_myeloma,_induction#RVDC|VDCR]] | + | *Induction [[Multiple_myeloma,_induction#VDC|VDC]] versus [[Multiple_myeloma,_induction#VDC|VDC-mod]] versus [[Multiple_myeloma,_induction#RVD|VDR]] versus [[Multiple_myeloma,_induction#RVDC|VDCR]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Aspirin]] 325 mg PO once per day | *[[Aspirin]] 325 mg PO once per day | ||
**[[Warfarin (Coumadin)]] or [[Enoxaparin (Lovenox)]] could be used based on physician discretion | **[[Warfarin (Coumadin)]] or [[Enoxaparin (Lovenox)]] could be used based on physician discretion | ||
Line 94: | Line 126: | ||
*[[Acyclovir (Zovirax)]] prophylaxis for Herpes zoster recommended | *[[Acyclovir (Zovirax)]] prophylaxis for Herpes zoster recommended | ||
*[[:Category:Bisphosphonates|Bisphosphonates]] could be used "as necessary" | *[[:Category:Bisphosphonates|Bisphosphonates]] could be used "as necessary" | ||
− | |||
'''42-day cycle for 4 cycles''' | '''42-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in abstract form at the 51st American Society of Hematology (ASH) annual meeting, New Orleans, LA, December 7, 2009; the 52nd ASH annual meeting, Orlando, FL, December 6, 2010; and the 13th International Myeloma Workshop, Paris, France, May 5, 2011.--> | <!-- Presented in abstract form at the 51st American Society of Hematology (ASH) annual meeting, New Orleans, LA, December 7, 2009; the 52nd ASH annual meeting, Orlando, FL, December 6, 2010; and the 13th International Myeloma Workshop, Paris, France, May 5, 2011.--> | ||
− | # '''EVOLUTION:''' Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. [ | + | # '''EVOLUTION:''' Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. [https://doi.org/10.1182/blood-2011-11-395749 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22422823/ PubMed] [https://clinicaltrials.gov/study/NCT00507442 NCT00507442] |
− | # '''NMSG 15/05:''' Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. Epub 2013 Apr 24. [ | + | # '''NMSG 15/05:''' Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. Epub 2013 Apr 24. [https://doi.org/10.1182/blood-2012-11-464503 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674665/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23616624/ PubMed] [https://clinicaltrials.gov/study/NCT00417911 NCT00417911] |
<!-- Presented at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011; and the 55th ASH Annual Meeting and Exposition, New Orleans, LA, December 7-10, 2013. --> | <!-- Presented at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011; and the 55th ASH Annual Meeting and Exposition, New Orleans, LA, December 7-10, 2013. --> | ||
− | # '''UPFRONT:''' Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol. 2015 Nov 20;33(33):3921-9. Epub 2015 Jun 8. [ | + | # '''UPFRONT:''' Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol. 2015 Nov 20;33(33):3921-9. Epub 2015 Jun 8. [https://doi.org/10.1200/jco.2014.58.7618 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26056177/ PubMed] [https://clinicaltrials.gov/study/NCT00507416 NCT00507416] |
− | + | # '''MMY-3012:''' Einsele H, Knop S, Vogel M, Müller J, Kropff M, Metzner B, Langer C, Sayer H, Jung W, Dürk HA, Salwender H, Wandt H, Bassermann F, Gramatzki M, Rösler W, Wolf HH, Brugger W, Engelhardt M, Fischer T, Liebisch P, Straka C. Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma. Leukemia. 2017 Jun;31(6):1463-1466. Epub 2017 Mar 15. [https://doi.org/10.1038/leu.2017.83 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28293022/ PubMed] [https://clinicaltrials.gov/study/NCT00416273 NCT00416273] | |
+ | # '''MMY-3013:''' Einsele H, Knop S, Vogel M, Müller J, Kropff M, Metzner B, Langer C, Sayer H, Jung W, Dürk HA, Salwender H, Wandt H, Bassermann F, Gramatzki M, Rösler W, Wolf HH, Brugger W, Engelhardt M, Fischer T, Liebisch P, Straka C. Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma. Leukemia. 2017 Jun;31(6):1463-1466. Epub 2017 Mar 15. [https://doi.org/10.1038/leu.2017.83 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28293022/ PubMed] [https://clinicaltrials.gov/study/NCT00416208 NCT00416208] | ||
==Bortezomib & Melphalan, then auto HSCT {{#subobject:9c28bc|Regimen=1}}== | ==Bortezomib & Melphalan, then auto HSCT {{#subobject:9c28bc|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bor-HDM: '''<u>Bor</u>'''tezomib, '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>M</u>'''elphalan | Bor-HDM: '''<u>Bor</u>'''tezomib, '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:0bfd33|Variant=1}}=== | ===Regimen {{#subobject:0bfd33|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2009-06-229658 Roussel et al. 2009] |
− | | style="background-color:#91cf61" |Phase | + | |2007-07 to 2007-12 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
{{#lst:Autologous HSCT|0bfd33}} | {{#lst:Autologous HSCT|0bfd33}} | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. [ | + | # Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. [https://doi.org/10.1182/blood-2009-06-229658 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19884643/ PubMed] [https://clinicaltrials.gov/study/NCT00642395 NCT00642395] |
==DCEP {{#subobject:431b08|Regimen=1}}== | ==DCEP {{#subobject:431b08|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
DCEP: '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin) | DCEP: '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:bbd0bf|Variant=1}}=== | ===Regimen {{#subobject:bbd0bf|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2009.27.9158 Harousseau et al. 2010 (IFM 2005-01)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |Observation | + | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] |
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR/nCR rate | + | |style="background-color:#ffffbf"|Did not meet composite primary endpoint of CR/nCR rate |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#Bortezomib_.26_Dexamethasone_. | + | *Induction [[Multiple_myeloma,_induction#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]] x 4 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 4 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m<sup>2</sup>) | *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m<sup>2</sup>) | ||
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m<sup>2</sup>) | *[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m<sup>2</sup>) | ||
*[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 60 mg/m<sup>2</sup>) | *[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 60 mg/m<sup>2</sup>) | ||
− | |||
'''28-day cycle for 2 cycles''' | '''28-day cycle for 2 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with autologous hematopoietic cell transplant]] consolidation |
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- Presented at the 48th Annual Meeting of the American Society of Hematology (ASH), December 9-12, 2006, Orlando, FL; the 49th Annual Meeting of the ASH, December 8-11, 2007, Atlanta, GA; the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30-June 3, 2008, Chicago, IL; and the 2008 Annual Meeting of the American Society of Hematology ASH/ASCO Joint Symposium, December 7, 2008, San Francisco, CA. --> | <!-- Presented at the 48th Annual Meeting of the American Society of Hematology (ASH), December 9-12, 2006, Orlando, FL; the 49th Annual Meeting of the ASH, December 8-11, 2007, Atlanta, GA; the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30-June 3, 2008, Chicago, IL; and the 2008 Annual Meeting of the American Society of Hematology ASH/ASCO Joint Symposium, December 7, 2008, San Francisco, CA. --> | ||
− | # '''IFM 2005-01:''' Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20;28(30):4621-9. Epub 2010 Sep 7. [ | + | # '''IFM 2005-01:''' Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20;28(30):4621-9. Epub 2010 Sep 7. [https://doi.org/10.1200/jco.2009.27.9158 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20823406/ PubMed] [https://clinicaltrials.gov/study/NCT00200681 NCT00200681] |
− | |||
==KTD {{#subobject:bc0c24|Regimen=1}}== | ==KTD {{#subobject:bc0c24|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | KTD: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 27/50/20 {{#subobject:bc14c4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ Sonneveld et al. 2014 (CARTHADEX)] | ||
+ | |2010-2013 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: this was the dosing for Cohort 1.'' | |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen {{#subobject: | + | ====Preceding treatment==== |
− | {| class="wikitable" style="width: | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with stem cell rescue]] consolidation |
− | !style="width: | + | </div> |
− | !style="width: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
+ | *[[Carfilzomib (Kyprolis)]] 27 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16 | ||
+ | *[[Thalidomide (Thalomid)]] 50 mg PO once per day | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycle for 4 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 36/50/20 {{#subobject:bcug14|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ Sonneveld et al. 2014 (CARTHADEX)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ Sonneveld et al. 2014 (CARTHADEX)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2010-2013 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: this was the dosing for Cohort 2.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with stem cell rescue]] consolidation |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Carfilzomib (Kyprolis)]] | + | *[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16 |
− | |||
− | |||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22 | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycle for 4 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- # '''Abstract:''' Pieter Sonneveld, Emilie Asselberg-Hacker, Sonja Zweegman, Bronno van der Holt, Marie Jose Kersten, Edo Vellenga, Marinus van Marwijk Kooy, Okke de Weerdt, Sarah Lonergan, Antonio Palumbo, Henk Lokhorst. Dose Escalation Phase 2 Trial Of Carfilzomib Combined With Thalidomide and Low-Dose Dexamethason In Newly Diagnosed, Transplant Eligible Patients With Multiple Myeloma. A Trial Of The European Myeloma Network. Blood Nov 2013,122(21)688 [https://doi.org/10.1182/blood.V122.21.688.688 link to abstract] --> | ||
+ | # '''CARTHADEX:''' Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. [https://doi.org/10.1182/blood-2014-05-576256 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25398935/ PubMed] NTR2422 | ||
+ | ==Melphalan monotherapy, then auto HSCT {{#subobject:263542|Regimen=1}}== | ||
+ | HDM: '''<u>H</u>'''igh-'''<u>D</u>'''ose '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#bebada"> | ||
+ | ===Synopsis=== | ||
+ | '''Development''' | ||
− | ''' | + | The concept of high-dose chemotherapy followed by ASCT emerged as a treatment modality for hematological malignancies in the 1980s. The rationale was to provide high doses of chemotherapy to eradicate malignant cells that were resistant to conventional doses. However, these high doses also destroyed the patient's bone marrow, necessitating a rescue with previously harvested and stored stem cells. Autologous transplantation uses the patient's own stem cells, harvested prior to the high-dose chemotherapy. |
+ | |||
+ | '''Clinical Trials & Evidence''' | ||
+ | |||
+ | [https://pubmed.ncbi.nlm.nih.gov/8649495/] Attal et al., 1996 (Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New England Journal of Medicine. 1996;335:91-7): In this landmark trial, patients with multiple myeloma were randomized to receive either standard chemotherapy or high-dose chemotherapy followed by ASCT. The results showed a higher response rate and prolonged event-free survival in the ASCT group. | ||
+ | |||
+ | [https://pubmed.ncbi.nlm.nih.gov/9864146/] Barlogie et al., 1999 (Barlogie B, Jagannath S, Vesole DH, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1999;93:1172-9): This study demonstrated the benefit of two consecutive ASCTs (tandem transplants) over a single transplant in patients with newly diagnosed multiple myeloma. | ||
+ | |||
+ | 2000s-2010s Trials: Further studies over these years demonstrated the sustained benefit of ASCT in multiple myeloma, especially when combined with novel agents like proteasome inhibitors, immunomodulatory agents, CD38 monoclonal antibodies, and corticosteroids. | ||
+ | |||
+ | '''Application in the Modern Era''' | ||
+ | |||
+ | 1. Induction Therapy: Before ASCT, patients receive induction therapy with a combination of drugs for cytoreduction. Modern regimens often include monoclonal antibodies (e.g., daratumumab), proteasome inhibitors (e.g., bortezomib or carfilzomib), immunomodulatory drugs (e.g., lenalidomide), and steroids (typically dexamethasone). | ||
+ | |||
+ | 2. Stem Cell Harvesting: Stem cells are collected from the patient’s peripheral blood after mobilization with growth factors, usually granulocyte colony-stimulating factor (G-CSF) often in combination with plerixafor. | ||
+ | |||
+ | 3. High-Dose Chemotherapy: Melphalan remains the standard conditioning agent for multiple myeloma. Patients receive high doses of melphalan, which kill myeloma cells but also suppress the bone marrow. | ||
+ | |||
+ | 4. Stem Cell Infusion: After chemotherapy, the previously harvested stem cells are infused back into the patient to "rescue" the bone marrow. | ||
+ | |||
+ | 5. Maintenance Therapy: Following recovery from ASCT, patients often receive maintenance therapy with agents like lenalidomide to prolong remission. | ||
− | + | '''Conclusion''' | |
− | |||
− | |||
− | + | High-dose chemotherapy followed by ASCT has significantly improved outcomes for patients with multiple myeloma over the past few decades. While newer therapies continue to emerge, ASCT remains an integral part of the treatment paradigm for eligible patients. | |
− | + | <br><small>''The draft for this synopsis was generated by a large language model and then manually edited by the page editor for accuracy and style. See [[Large language model pilot|this page]] for more information about this pilot project.''</small> | |
− | + | </div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 140 mg/m<sup>2</sup> {{#subobject:255748|Variant=1}}=== | ===Regimen variant #1, 140 mg/m<sup>2</sup> {{#subobject:255748|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.V67.5.1298.1298 Barlogie et al. 1986] |
− | | style="background-color:#ffffbe" |Non-randomized, | + | |Not reported |
+ | | style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -2 & -1 | *[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -2 & -1 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 200 mg/m<sup>2</sup> {{#subobject:3d1bf6|Variant=1}}=== | ===Regimen variant #2, 200 mg/m<sup>2</sup> {{#subobject:3d1bf6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2005-03-1301 Bladé et al. 2005] |
|1994-1999 | |1994-1999 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#VBMCP.2FVBAD|VBMCP/VBAD]] | |[[#VBMCP.2FVBAD|VBMCP/VBAD]] | ||
|style="background-color:#ffffbf"|Did not meet efficacy endpoint | |style="background-color:#ffffbf"|Did not meet efficacy endpoint | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.v99.3.731 Moreau et al. 2002 (IFM 9502)] |
|1995-1999 | |1995-1999 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-de-esc) |
|[[Multiple_myeloma_-_historical#Melphalan_.2B_TBI.2C_then_auto_HSCT|Melphalan & TBI, then auto HSCT]] | |[[Multiple_myeloma_-_historical#Melphalan_.2B_TBI.2C_then_auto_HSCT|Melphalan & TBI, then auto HSCT]] | ||
− | |style="background-color:# | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2006.10.2509 Cavo et al. 2007 (Bologna 96)] |
|1996-2001 | |1996-2001 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[Multiple_myeloma_-_historical# | + | |[[Multiple_myeloma_-_historical#Melphalan_monotherapy.2C_then_auto HSCT.2C_then_Melphalan_.26_Busulfan.2C_then_auto HSCT|Melphalan, then auto HSCT, then Melphalan & Busulfan, then auto HSCT]] |
|style="background-color:#d73027"|Inferior EFS | |style="background-color:#d73027"|Inferior EFS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/bjh.13994 Mai et al. 2016 (GMMG-HD2)] |
|1998-2002 | |1998-2002 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem melphalan, then auto HSCT]] | |[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem melphalan, then auto HSCT]] | ||
|style="background-color:#eeee01"|Non-inferior EFS | |style="background-color:#eeee01"|Non-inferior EFS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2009-05-222539 Lokhorst et al. 2009 (HOVON-50)] |
|2001-2005 | |2001-2005 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
Line 254: | Line 342: | ||
|[https://doi.org/10.1200/jco.2010.32.7312 Björkstrand et al. 2011 (EBMT-NMAM2000)] | |[https://doi.org/10.1200/jco.2010.32.7312 Björkstrand et al. 2011 (EBMT-NMAM2000)] | ||
|2001-2005 | |2001-2005 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |MEL200, then auto HSCT, then RIC allo HSCT | + | |[[#Melphalan_monotherapy.2C_then_auto_HSCT|MEL200, then auto HSCT]], then RIC allo HSCT |
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639680/ Morgan et al. 2010 (MRC Myeloma IX)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639680/ Morgan et al. 2010 (MRC Myeloma IX)] | ||
|2003-2007 | |2003-2007 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (HOVON-65)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2012-02-408922 Rosiñol et al. 2012 (GEM05/MENOS65)] |
|2006-2009 | |2006-2009 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-05-355081 Moreau et al. 2011 (IFM 2007-02)] |
− | |2008-2009 | + | |2008-03 to 2009-01 |
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2013.54.8164 Roussel et al. 2014 (IFM 2008)] |
|2009 | |2009 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1038/leu.2015.80 Mai et al. 2015 (GMMG-MM5)] |
− | | | + | |2010-2012 |
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ Attal et al. 2017 (IFM 2009)] | ||
+ | |2010-2012 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#RVD|RVD]] consolidation | ||
+ | |style="background-color:#1a9850"|Superior PFS<br>Median PFS: 50 vs 36 mo<br>(HR 0.65, 95% CI 0.53-0.80) | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ Sonneveld et al. 2014 (CARTHADEX)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ Sonneveld et al. 2014 (CARTHADEX)] | ||
− | | | + | |2010-2013 |
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553842/ Stadtmauer et al. 2019 (STAMINA)] |
− | | | + | |2010-2013 |
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#1a9851"|Phase 3 (C) |
+ | |1. [[#Tandem_melphalan.2C_then_auto_HSCT|Tandem melphalan, then auto HSCT]]<br>2. [[#Melphalan_monotherapy.2C_then_auto_HSCT|MEL200, then auto HSCT]], then [[#RVD|RVD]] consolidation | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS38 | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040899/ Richardson et al. 2022 (DETERMINATION)] | ||
+ | |2010-10-01 to 2018-01-30 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#RVD|RVD]] consolidation | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 67.5 vs 46.2 mo<br>(HR 0.65, 95% CI 0.52-0.81) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943328/ Lok et al. 2014] | ||
+ | |2011-2013 | ||
+ | |style="background-color:#91cf61"|Non-randomized | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446704/ Bashir et al. 2019 (MDACC 2010-0071)] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|2011-2017 | |2011-2017 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |Bu/Mel, then auto HSCT | + | |[[#Busulfan_.26_Melphalan.2C_then_auto_HSCT_888|Bu/Mel, then auto HSCT]] |
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1182/blood.2021014635 Roussel et al. 2022 (IFM 2014-02)] | ||
+ | |2015-01-21 to 2016-09-21 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Bortezomib_.26_Melphalan.2C_then_auto_HSCT_888|Bor-HDM, then auto HSCT]] | ||
+ | |style="background-color:#ffffbf"|Did not meet composite primary endpoint of sCR/CR rate at day +60 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *IFM 9502: [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 | + | *IFM 9502: Induction [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 |
− | *Bladé et al. 2005: [[Multiple_myeloma_-_historical#VBMCP.2FVBAD|VBMCP/VBAD]] x 4 | + | *Bladé et al. 2005: Induction [[Multiple_myeloma_-_historical#VBMCP.2FVBAD|VBMCP/VBAD]] x 4 |
− | *Bologna 96: [[Multiple_myeloma_-_historical#VAD|VAD]] x 4 | + | *Bologna 96: Induction [[Multiple_myeloma_-_historical#VAD|VAD]] x 4 |
− | *HOVON-50: [[Multiple_myeloma,_induction#TAD|TAD]] x 3 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 | + | *HOVON-50: Induction [[Multiple_myeloma,_induction#TAD|TAD]] x 3 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 |
− | * | + | *IFM 2007-02: Induction [[Multiple_myeloma,_induction#VTD|vtD]] x 4 versus [[Multiple_myeloma,_induction#Bortezomib_.26_Dexamethasone_.28Vd.29|Vd]] x 4 |
− | *MRC Myeloma IX: [[Multiple_myeloma,_induction#CTD|CTD]] x 4 to 6 versus [[Multiple_myeloma,_induction#CVAD|CVAD]] x 4 to 6 | + | *MRC Myeloma IX: Induction [[Multiple_myeloma,_induction#CTD|CTD]] x 4 to 6 versus [[Multiple_myeloma,_induction#CVAD|CVAD]] x 4 to 6 |
− | *GEM05/MENOS65: [[Multiple_myeloma,_induction# | + | *GEM05/MENOS65: Induction [[Multiple_myeloma,_induction#Thalidomide_.26_Dexamethasone_.28TD.29|TD]] x 6 versus VBMCP/VBAD/B x 6 versus [[Multiple_myeloma,_induction#VTD|VTD]] x 6 |
− | *HOVON-65: [[Multiple_myeloma,_induction#PAD|PAD]] x 3 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 | + | *HOVON-65: Induction [[Multiple_myeloma,_induction#PAD|PAD]] x 3 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 |
− | *Lok et al. 2014: [[Multiple_myeloma,_induction#VTD|vtD]] x 4 | + | *Lok et al. 2014: Induction [[Multiple_myeloma,_induction#VTD|vtD]] x 4 |
− | *IFM 2008: [[Multiple_myeloma,_induction#RVD|RVD]] x 3 | + | *IFM 2008: Induction [[Multiple_myeloma,_induction#RVD|RVD]] x 3 |
− | *CARTHADEX: [[Multiple_myeloma,_induction#KTD|KTD]] x 4 | + | *CARTHADEX: Induction [[Multiple_myeloma,_induction#KTD|KTD]] x 4 |
− | *GMMG-MM5: [[Multiple_myeloma,_induction#VDC|VCD]] x 3 versus [[Multiple_myeloma,_induction#PAD|PAd]] x 3 | + | *GMMG-MM5: Induction [[Multiple_myeloma,_induction#VDC|VCD]] x 3 versus [[Multiple_myeloma,_induction#PAD|PAd]] x 3 |
− | *IFM 2009: [[Multiple_myeloma,_induction#RVD|RVD]] x 3 | + | *IFM 2009 & DETERMINATION: Induction [[Multiple_myeloma,_induction#RVD|RVD]] x 3 |
+ | *IFM 2014-02: Induction [[Multiple_myeloma,_induction#VTD|VTd]] or [[Multiple_myeloma,_induction#VDC|CyBorD]] or [[Multiple_myeloma,_induction#RVD|RVd]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2 | *[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *IFM 9502: [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]] x 12 mo | + | *IFM 9502: [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]] maintenance x 12 mo |
− | *Bladé et al. 2005: [[Multiple_myeloma_-_historical#Interferon_alfa_.26_Dexamethasone|IFN & Dexamethasone | + | *Bladé et al. 2005: [[Multiple_myeloma_-_historical#Interferon_alfa_.26_Dexamethasone|IFN & Dexamethasone]] maintenance |
− | *Bologna 96 | + | *Bologna 96: [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]] maintenance |
− | *HOVON-50 | + | *HOVON-50, induced with VAD: [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]] maintenance |
− | *MRC Myeloma IX: [[#Thalidomide_monotherapy|Thalidomide | + | *HOVON-50, induced with TAD: [[#Thalidomide_monotherapy|Thalidomide]] maintenance |
− | *GEM05/MENOS65:[[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa-2b]] x 36 mo versus [[#Thalidomide_monotherapy|Thalidomide]] x 36 mo versus [[#VT|TV]] x 36 mo | + | *MRC Myeloma IX: [[#Thalidomide_monotherapy|Thalidomide]] maintenance versus [[Multiple_myeloma_-_null_regimens#Observation|no further treatment]] |
− | *HOVON-65 | + | *GEM05/MENOS65: [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa-2b]] maintenance x 36 mo versus [[#Thalidomide_monotherapy|Thalidomide]] x 36 mo versus [[#VT|TV]] x 36 mo |
− | *HOVON-65 | + | *HOVON-65, induced with PAD: [[#Bortezomib_monotherapy_2|Bortezomib]] maintenance x 24 mo |
− | *Lok et al. 2014: [[#VTD|vtD | + | *HOVON-65, induced with VAD: [[#Thalidomide_monotherapy|Thalidomide]] maintenance x 24 mo |
− | *IFM 2008 & IFM 2009: [[#RVD|RVD | + | *Lok et al. 2014 & IFM 2014-02: [[#VTD|vtD]] consolidation x 2 |
− | *CARTHADEX: [[#KTD|KTD | + | *IFM 2008 & IFM 2009: [[#RVD|RVD]] consolidation x 2 |
− | *GMMG-MM5, if at least nCR not achieved: [[# | + | *CARTHADEX: [[#KTD|KTD]] consolidation x 4 |
− | *GMMG-MM5, at least nCR achieved: [[#Lenalidomide_monotherapy|Lenalidomide]] x 24 mo vs [[#Lenalidomide_monotherapy|Lenalidomide]] until CR | + | *GMMG-MM5, if at least nCR not achieved: [[#Melphalan_monotherapy.2C_then_auto_HSCT|MEL200, then auto HSCT]] |
+ | *GMMG-MM5, at least nCR achieved: [[#Lenalidomide_monotherapy|Lenalidomide]] maintenance x 24 mo vs [[#Lenalidomide_monotherapy|Lenalidomide]] until CR | ||
+ | *DETERMINATION: [[#Lenalidomide_monotherapy|Lenalidomide]] maintenance | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. [ | + | # Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. [https://doi.org/10.1182/blood.V67.5.1298.1298 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3516252/ PubMed] |
− | # '''IFM 9502:''' Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, François S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL; Intergroupe Francophone du Myélome. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002 Feb 1;99(3):731-5. [ | + | # '''IFM 9502:''' Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, François S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL; Intergroupe Francophone du Myélome. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002 Feb 1;99(3):731-5. [https://doi.org/10.1182/blood.v99.3.731 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11806971/ PubMed] |
− | # Bladé J, Rosiñol L, Sureda A, Ribera JM, Díaz-Mediavilla J, García-Laraña J, Mateos MV, Palomera L, Fernández-Calvo J, Martí JM, Giraldo P, Carbonell F, Callís M, Trujillo J, Gardella S, Moro MJ, Barez A, Soler A, Font L, Fontanillas M, San Miguel J; PETHEMA. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005 Dec 1;106(12):3755-9. Epub 2005 Aug 16. [ | + | # Bladé J, Rosiñol L, Sureda A, Ribera JM, Díaz-Mediavilla J, García-Laraña J, Mateos MV, Palomera L, Fernández-Calvo J, Martí JM, Giraldo P, Carbonell F, Callís M, Trujillo J, Gardella S, Moro MJ, Barez A, Soler A, Font L, Fontanillas M, San Miguel J; PETHEMA. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005 Dec 1;106(12):3755-9. Epub 2005 Aug 16. [https://doi.org/10.1182/blood-2005-03-1301 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16105975/ PubMed] |
− | # '''Bologna 96:''' Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, Di Raimondo F, Volpe E, Ronconi S, Cangini D, Narni F, Carubelli A, Masini L, Catalano L, Fiacchini M, de Vivo A, Gozzetti A, Lazzaro A, Tura S, Baccarani M. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007 Jun 10;25(17):2434-41. Epub 2007 May 7. [ | + | # '''Bologna 96:''' Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, Di Raimondo F, Volpe E, Ronconi S, Cangini D, Narni F, Carubelli A, Masini L, Catalano L, Fiacchini M, de Vivo A, Gozzetti A, Lazzaro A, Tura S, Baccarani M. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007 Jun 10;25(17):2434-41. Epub 2007 May 7. [https://doi.org/10.1200/jco.2006.10.2509 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17485707/ PubMed] [https://clinicaltrials.gov/study/NCT00378222 NCT00378222] |
<!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. --> | <!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. --> | ||
− | # '''HOVON-50:''' Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; HOVON. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [ | + | # '''HOVON-50:''' Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; HOVON. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [https://doi.org/10.1182/blood-2009-05-222539 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19880501/ PubMed] [https://clinicaltrials.gov/study/NCT00028886 NCT00028886] |
− | ## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https:// | + | ## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905/ PubMed] |
− | # '''MRC Myeloma IX:''' Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. [https:// | + | # '''MRC Myeloma IX:''' Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. [https://doi.org/10.1016/S0140-6736(10)62051-X link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21131037/ PubMed] ISRCTN68454111 |
− | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. [ | + | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. [https://doi.org/10.1182/blood-2011-02-338665 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21652683/ PubMed] |
− | ## '''Update:''' Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5;119(1):7-15. Epub 2011 Oct 20. [ | + | ## '''Update:''' Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5;119(1):7-15. Epub 2011 Oct 20. [https://doi.org/10.1182/blood-2011-06-357038 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22021371/ PubMed] |
− | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. [ | + | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. [https://doi.org/10.3324/haematol.2011.043372 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291601/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22058209/ PubMed] |
− | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. [ | + | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. [https://doi.org/10.1158/1078-0432.CCR-12-3211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23995858/ PubMed] |
− | # '''EBMT-NMAM2000:''' Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. [https://doi.org/10.1200/jco.2010.32.7312 link to original article] ''' | + | # '''EBMT-NMAM2000:''' Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. [https://doi.org/10.1200/jco.2010.32.7312 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21730266/ PubMed] |
− | ## '''Update:''' Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. [ | + | ## '''Update:''' Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. [https://doi.org/10.1182/blood-2012-11-469452 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23482933/ PubMed] |
− | # '''IFM 2007-02:''' Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. [ | + | # '''IFM 2007-02:''' Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. [https://doi.org/10.1182/blood-2011-05-355081 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21849487/ PubMed] [https://clinicaltrials.gov/study/NCT00910897 NCT00910897] |
− | + | # '''GEM05/MENOS65:''' Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. [https://doi.org/10.1182/blood-2012-02-408922 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22791289/ PubMed] [https://clinicaltrials.gov/study/NCT00461747 NCT00461747] | |
− | ## '''Update:''' Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. [https://doi.org/10.1038/leu.2017.35 link to original article] ''' | + | ## '''Update:''' Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. [https://doi.org/10.1038/leu.2017.35 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28111466/ PubMed] |
− | # '''HOVON-65 | + | # '''HOVON-65:''' Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. [https://doi.org/10.1200/jco.2011.39.6820 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22802322/ PubMed] ISRCTN64455289 |
− | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [ | + | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [https://doi.org/10.1182/blood-2011-09-379164 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22160383/ PubMed] |
− | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https:// | + | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https://doi.org/10.1038/leu.2017.211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28761118/ PubMed] |
− | # Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous bortezomib incorporated into the bortezomib-thalidomide-dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. [ | + | # Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous bortezomib incorporated into the bortezomib-thalidomide-dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. [https://doi.org/10.3324/haematol.2013.100396 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943328/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24532044/ PubMed] |
− | # '''IFM 2008:''' Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. [ | + | # '''IFM 2008:''' Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. [https://doi.org/10.1200/jco.2013.54.8164 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25024076/ PubMed] [https://clinicaltrials.gov/study/NCT01206205 NCT01206205] |
− | <!-- # '''Abstract:''' Pieter Sonneveld, Emilie Asselberg-Hacker, Sonja Zweegman, Bronno van der Holt, Marie Jose Kersten, Edo Vellenga, Marinus van Marwijk Kooy, Okke de Weerdt, Sarah Lonergan, Antonio Palumbo, Henk Lokhorst. Dose Escalation Phase 2 Trial Of Carfilzomib Combined With Thalidomide and Low-Dose Dexamethason In Newly Diagnosed, Transplant Eligible Patients With Multiple Myeloma. A Trial Of The European Myeloma Network. Blood Nov 2013,122(21)688 [ | + | <!-- # '''Abstract:''' Pieter Sonneveld, Emilie Asselberg-Hacker, Sonja Zweegman, Bronno van der Holt, Marie Jose Kersten, Edo Vellenga, Marinus van Marwijk Kooy, Okke de Weerdt, Sarah Lonergan, Antonio Palumbo, Henk Lokhorst. Dose Escalation Phase 2 Trial Of Carfilzomib Combined With Thalidomide and Low-Dose Dexamethason In Newly Diagnosed, Transplant Eligible Patients With Multiple Myeloma. A Trial Of The European Myeloma Network. Blood Nov 2013,122(21)688 [https://doi.org/10.1182/blood.V122.21.688.688 link to abstract] --> |
− | # '''CARTHADEX:''' Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. [ | + | # '''CARTHADEX:''' Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. [https://doi.org/10.1182/blood-2014-05-576256 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300390/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25398935/ PubMed] NTR2422 |
− | # '''GMMG-MM5:''' Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, Munder M, Jauch A, Schurich B, Hielscher T, Merz M, Huegle-Doerr B, Seckinger A, Hose D, Hillengass J, Raab MS, Neben K, Lindemann HW, Zeis M, Gerecke C, Schmidt-Wolf IG, Weisel K, Scheid C, Salwender H, Goldschmidt H. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015 Aug;29(8):1721-9. Epub 2015 Mar 19. [https://doi.org/10.1038/leu.2015.80 link to original article] ''' | + | # '''GMMG-MM5:''' Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, Munder M, Jauch A, Schurich B, Hielscher T, Merz M, Huegle-Doerr B, Seckinger A, Hose D, Hillengass J, Raab MS, Neben K, Lindemann HW, Zeis M, Gerecke C, Schmidt-Wolf IG, Weisel K, Scheid C, Salwender H, Goldschmidt H. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015 Aug;29(8):1721-9. Epub 2015 Mar 19. [https://doi.org/10.1038/leu.2015.80 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25787915/ PubMed] EudraCT 2010-019173-16 |
− | ## ''' | + | ## '''Subgroup analysis:''' Merz M, Salwender H, Haenel M, Mai EK, Bertsch U, Kunz C, Hielscher T, Blau IW, Scheid C, Hose D, Seckinger A, Jauch A, Hillengass J, Raab MS, Schurich B, Munder M, Schmidt-Wolf IG, Gerecke C, Lindemann HW, Zeis M, Weisel K, Duerig J, Goldschmidt H. Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial. Haematologica. 2015 Jul;100(7):964-9. Epub 2015 Apr 3. [https://doi.org/10.3324/haematol.2015.124347 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486231/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25840597/ PubMed] |
− | + | ## '''Update:''' Goldschmidt H, Mai EK, Dürig J, Scheid C, Weisel KC, Kunz C, Bertsch U, Hielscher T, Merz M, Munder M, Lindemann HW, Hügle-Dörr B, Tichy D, Giesen N, Hose D, Seckinger A, Huhn S, Luntz S, Jauch A, Elmaagacli A, Rabold B, Fuhrmann S, Brossart P, Goerner M, Bernhard H, Hoffmann M, Hillengass J, Raab MS, Blau IW, Hänel M, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG). Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. Leukemia. 2020 Jul;34(7):1853-1865. Epub 2020 Feb 7. [https://doi.org/10.1038/s41375-020-0724-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32034285/ PubMed] | |
− | # ''' | + | # '''GMMG-HD2:''' Mai EK, Benner A, Bertsch U, Brossart P, Hänel A, Kunzmann V, Naumann R, Neben K, Egerer G, Ho AD, Hillengass J, Raab MS, Neubauer A, Peyn A, Ko YD, Peter N, Scheid C, Goldschmidt H. Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial. Br J Haematol. 2016 Jun;173(5):731-41. Epub 2016 Mar 17. [https://doi.org/10.1111/bjh.13994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26990892/ PubMed] DRKS00008864 |
− | # ''' | + | # '''IFM 2009:''' Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. [https://doi.org/10.1056/NEJMoa1611750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28379796/ PubMed] [https://clinicaltrials.gov/study/NCT01191060 NCT01191060] |
− | # ''' | + | # '''STAMINA:''' Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, Efebera Y, Ganguly S, Gasparetto C, Geller N, Horowitz MM, Koreth J, Knust K, Landau H, Brunstein C, McCarthy P, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Giralt S, Somlo G, Krishnan A. Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial. J Clin Oncol. 2019 Mar 1;37(7):589-597. Epub 2019 Jan 17. [https://doi.org/10.1200/JCO.18.00685 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553842/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30653422/ PubMed] [https://clinicaltrials.gov/study/NCT01109004 NCT01109004] |
+ | # '''MDACC 2010-0071:''' Bashir Q, Thall PF, Milton DR, Fox PS, Kawedia JD, Kebriaei P, Shah N, Patel K, Andersson BS, Nieto YL, Valdez BC, Parmar S, Rondon G, Delgado R, Hosing C, Popat UR, Oran B, Ciurea SO, Lin P, Weber DM, Thomas SK, Lee HC, Manasanch EE, Orlowski RZ, Williams LA, Champlin RE, Qazilbash MH. Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial. Lancet Haematol. 2019 May;6(5):e266-e275. Epub 2019 Mar 22. [https://doi.org/10.1016/S2352-3026(19)30023-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446704/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30910541/ PubMed] [https://clinicaltrials.gov/study/NCT01413178 NCT01413178] | ||
+ | # '''EMN02/HOVON-95:''' Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. [https://doi.org/10.1016/s2352-3026(20)30099-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32359506/ PubMed] [https://clinicaltrials.gov/study/NCT01208766 NCT01208766] | ||
+ | ## '''Update:''' Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. [https://doi.org/10.1200/jco.21.01045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34520219/ PubMed] | ||
+ | #'''IFM 2014-02:''' Roussel M, Lauwers-Cances V, Macro M, Leleu X, Royer B, Hulin C, Karlin L, Perrot A, Touzeau C, Chrétien ML, Rigaudeau S, Dib M, Nicolas-Virelizier E, Escoffre-Barbe M, Belhadj K, Mariette C, Stoppa AM, Araujo C, Doyen C, Fontan J, Kolb B, Garderet L, Brechignac S, Malfuson JV, Jaccard A, Lenain P, Borel C, Hebraud B, Benbrahim O, Dorvaux V, Manier S, Augeul-Meunier K, Vekemans MC, Randriamalala E, Chaoui D, Caers J, Chaleteix C, Benboubker L, Vincent L, Glaisner S, Zunic P, Slama B, Eveillard JR, Humbrecht-Kraut C, Morel V, Mineur P, Eisenmann JC, Demarquette H, Richez V, Vignon M, Caillot D, Facon T, Moreau P, Colin AL, Olivier P, Wuilleme S, Avet-Loiseau H, Corre J, Attal M. Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study. Blood. 2022 May 5;139(18):2747-2757. [https://doi.org/10.1182/blood.2021014635 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35511184/ PubMed] [https://clinicaltrials.gov/study/NCT02197221 NCT02197221] | ||
+ | #'''DETERMINATION:''' Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2204925 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040899/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35660812/ PubMed] [https://clinicaltrials.gov/study/NCT01208662 NCT01208662] | ||
==MPR {{#subobject:611aa1|Regimen=1}}== | ==MPR {{#subobject:611aa1|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MPR: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>R</u>'''evlimid (Lenalidomide) | MPR: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>R</u>'''evlimid (Lenalidomide) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 0.18/2/10 {{#subobject:eac77a|Variant=1}}=== | ===Regimen variant #1, 0.18/2/10 {{#subobject:eac77a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1402888 Palumbo et al. 2014 (MPRvsMEL200)] |
|2007-2009 | |2007-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem Melphalan, then auto HSCT]] | |[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem Melphalan, then auto HSCT]] | ||
|style="background-color:#fc8d59"|Seems to have inferior OS | |style="background-color:#fc8d59"|Seems to have inferior OS | ||
Line 412: | Line 524: | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *[[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] induction x 4 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 0.18 mg/kg PO once per day on days 1 to 4 | *[[Melphalan (Alkeran)]] 0.18 mg/kg PO once per day on days 1 to 4 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4 | *[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycle for 6 cycles''' | '''28-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Lenalidomide_monotherapy|Lenalidomide | + | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance versus [[Multiple_myeloma_-_null_regimens#Observation|no further treatment]] |
− | + | </div></div><br> | |
− | ===Regimen variant #2 {{#subobject:bd5044|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, 2/50/10 {{#subobject:bd5044|Variant=1}}=== |
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1038/leu.2012.271 Falco et al. 2012] | |[https://doi.org/10.1038/leu.2012.271 Falco et al. 2012] | ||
|2008-2009 | |2008-2009 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
''Note: this is a component of the sequential "RP-MPR-RP" protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of the sequential "RP-MPR-RP" protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *[[Multiple_myeloma,_induction#Lenalidomide_.26_Prednisone_.28RP.29|RP]] induction x 4 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 2 mg PO three times per week | *[[Melphalan (Alkeran)]] 2 mg PO three times per week | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 50 mg PO three times per week | *[[Prednisone (Sterapred)]] 50 mg PO three times per week | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Lenalidomide (Revlimid)]] 10 | + | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *Thromboprophylaxis: [[Aspirin]] 100 mg PO once per day, taken during lenalidomide treatment (unclear from protocol if this also means off weeks) |
− | *Thromboprophylaxis: [[Aspirin]] 100 mg PO once per day, taken during | ||
*Antiviral prophylaxis if history of VZV. | *Antiviral prophylaxis if history of VZV. | ||
− | |||
'''28-day cycle for 6 cycles''' | '''28-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[# | + | *[[#Lenalidomide_.26_Prednisone_.28RP.29_2|RP]] maintenance |
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #3, 2/50/15 {{#subobject:bd5043|Variant=1}}=== | |
− | + | {| class="wikitable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
+ | |- | ||
+ | |[https://doi.org/10.1038/leu.2012.271 Falco et al. 2012] | ||
+ | |2008-2009 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''Note: this is a component of the sequential "RP-MPR-RP" protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Multiple_myeloma,_induction#Lenalidomide_.26_Prednisone_.28RP.29|RP]] induction x 4 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Melphalan (Alkeran)]] 2 mg PO three times per week | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Prednisone (Sterapred)]] 50 mg PO three times per week | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21 | ||
+ | ====Supportive therapy==== | ||
+ | *Thromboprophylaxis: [[Aspirin]] 100 mg PO once per day, taken during lenalidomide treatment (unclear from protocol if this also means off weeks) | ||
+ | *Antiviral prophylaxis if history of VZV. | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Lenalidomide_.26_Prednisone_.28RP.29_2|RP]] maintenance | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Falco P, Cavallo F, Larocca A, Rossi D, Guglielmelli T, Rocci A, Grasso M, Siez ML, De Paoli L, Oliva S, Molica S, Mina R, Gay F, Benevolo G, Musto P, Omedè P, Freilone R, Bringhen S, Carella AM, Gaidano G, Boccadoro M, Palumbo A. Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. 2013 Mar;27(3):695-701. Epub 2012 Sep 21. [https://doi.org/10.1038/leu.2012.271 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22996335/ PubMed] | ||
+ | # '''MPRvsMEL200:''' Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. [https://doi.org/10.1056/NEJMoa1402888 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25184862/ PubMed] [https://clinicaltrials.gov/study/NCT00551928 NCT00551928] | ||
+ | ==Lenalidomide & Prednisone (RP) {{#subobject:ceb412|Regimen=1}}== | ||
RP: '''<u>R</u>'''evlimid (Lenalidomide) & '''<u>P</u>'''rednisone | RP: '''<u>R</u>'''evlimid (Lenalidomide) & '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:7d2a7c|Variant=1}}=== | ===Regimen {{#subobject:7d2a7c|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2009.22.7561 Palumbo et al. 2010] |
− | |style="background-color:#91cf61"|Phase | + | |2005-2007 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem MEL-100, then auto HSCT]] | + | *[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem MEL-100, then auto HSCT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 50 mg PO once every other day | *[[Prednisone (Sterapred)]] 50 mg PO once every other day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Aspirin]] 100 mg PO once per day during lenalidomide treatment |
− | *[[Aspirin]] 100 mg PO once per day during | ||
− | |||
'''28-day cycle for 4 cycles''' | '''28-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Lenalidomide_monotherapy|Lenalidomide | + | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [ | + | # Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [https://doi.org/10.1200/jco.2009.22.7561 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20048187/ PubMed] EudraCT 2005-004714-32 |
− | ## '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [ | + | ## '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [https://doi.org/10.1182/blood-2013-02-483073 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23775712/ PubMed] |
− | |||
==RVD {{#subobject:3d2d57|Regimen=1}}== | ==RVD {{#subobject:3d2d57|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone | RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone | ||
<br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide) | <br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide) | ||
<br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone | <br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone | ||
<br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | <br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 2 cycles post-transplant with lower-dose dex {{#subobject:073d3b|Variant=1}}=== | ===Regimen variant #1, 2 cycles post-transplant with lower-dose dex {{#subobject:073d3b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ Attal et al. 2017 (IFM 2009)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2010-2012 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic stem cell transplant]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | *[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Lenalidomide_monotherapy|Lenalidomide maintenance]] | + | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance |
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, 2 cycles with intermediate-dose dex {{#subobject:0h4d3b|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s2352-3026(20)30099-5 Cavo et al. 2020 (EMN02/HOVON-95)] | ||
+ | |2011-2014 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Multiple_myeloma_-_null_regimens#No_consolidation|No further]] consolidation | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 59.3 vs 42.9 mo<br>(HR 0.81, 95% CI 0.68-0.96) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[#VMP|VMP]] consolidation x 4 versus [[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic stem cell transplant]] x 1 to 2 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
+ | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV or SC once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | ||
+ | '''28-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 2 cycles post-transplant with higher-dose dex {{#subobject:073d3b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2013.54.8164 Roussel et al. 2014 (IFM 2008)] |
− | |style="background-color:#91cf61"|Phase | + | |2009 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Two months after hematologic recovery, patients without progressive disease began treatment.'' | ''Two months after hematologic recovery, patients without progressive disease began treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic stem cell transplant]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[:Category:Low_molecular_weight_heparins |Low–molecular weight heparin (LMWH)]] for DVT prophylaxis | *[[:Category:Low_molecular_weight_heparins |Low–molecular weight heparin (LMWH)]] for DVT prophylaxis | ||
*[[:Category:Antivirals |Antiviral therapy]] with example [[Valacyclovir (Valtrex) | valacyclovir]] given, for herpes zoster prevention | *[[:Category:Antivirals |Antiviral therapy]] with example [[Valacyclovir (Valtrex) | valacyclovir]] given, for herpes zoster prevention | ||
*[[:Category:Antibacterials |Antibiotic prophylaxis]] with example [[Amoxicillin | amoxicillin]] given, for bacterial infections | *[[:Category:Antibacterials |Antibiotic prophylaxis]] with example [[Amoxicillin | amoxicillin]] given, for bacterial infections | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Lenalidomide_monotherapy|Lenalidomide | + | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance |
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #4, 5 cycles, no transplant {{#subobject:073d3b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ Attal et al. 2017 (IFM 2009)] |
|2010-2012 | |2010-2012 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-de-esc) |
− | |[[#Melphalan.2C_then_auto_HSCT|Melphalan, then auto HSCT]] | + | |[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan, then auto HSCT]] |
− | |style="background-color:#d73027"|Inferior PFS | + | |style="background-color:#d73027"|Inferior PFS (primary endpoint) |
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040899/ Richardson et al. 2022 (DETERMINATION)] | ||
+ | |2010-10-01 to 2018-01-30 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan, then auto HSCT]] | ||
+ | |style="background-color:#d73027"|Inferior PFS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#RVD|RVD | + | *[[Multiple_myeloma,_induction#RVD|RVD]] induction x 3 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | ||
+ | '''21-day cycle for 5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 5 cycles, no transplant, SC bortezomib {{#subobject:073d3s|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040899/ Richardson et al. 2022 (DETERMINATION)] | ||
+ | |2010-10-01 to 2018-01-30 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan, then auto HSCT]] | ||
+ | |style="background-color:#d73027"|Inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Multiple_myeloma,_induction#RVD|RVD]] induction x 3 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14 | ||
+ | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | *[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | ||
− | |||
'''21-day cycle for 5 cycles''' | '''21-day cycle for 5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Lenalidomide_monotherapy|Lenalidomide | + | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance |
− | + | </div></div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #6, 8 cycles, no transplant {{#subobject:7fe92b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030380/ Jacobus et al. 2016 (E1A05)] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030380/ Jacobus et al. 2016 (ECOG E1A05)] |
|2008-2010 | |2008-2010 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |Rd | + | |[[#Lenalidomide_.26_Dexamethasone_.28Rd.29_888|Rd]] |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|} | |} | ||
''Note: this trial closed early due to poor accrual so only descriptive results are available.'' | ''Note: this trial closed early due to poor accrual so only descriptive results are available.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Dexamethasone-based induction | + | *[[Regimen_classes#Dexamethasone_based_regimen|Dexamethasone-based]] induction x 1 to 6 cycles |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14 | *[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14 | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15 | ||
− | |||
'''21-day cycle for 8 cycles''' | '''21-day cycle for 8 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''Retrospective:''' Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. [https://doi.org/10.1038/leu.2013.335 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24220275 PubMed] | + | # '''Retrospective:''' Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. [https://doi.org/10.1038/leu.2013.335 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24220275/ PubMed] |
− | # '''IFM 2008:''' Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. [ | + | # '''IFM 2008:''' Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. [https://doi.org/10.1200/jco.2013.54.8164 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25024076/ PubMed] [https://clinicaltrials.gov/study/NCT01206205 NCT01206205] |
− | # '''E1A05:''' Jacobus SJ, Rajkumar SV, Weiss M, Stewart AK, Stadtmauer EA, Callander NS, Dreosti LM, Lacy MQ, Fonseca R. Randomized phase III trial of consolidation therapy with bortezomib-lenalidomide-Dexamethasone (VRd) vs bortezomib-dexamethasone (Vd) for patients with multiple myeloma who have completed a dexamethasone based induction regimen. Blood Cancer J. 2016 Jul 29;6(7):e448. [https:// | + | # '''ECOG E1A05:''' Jacobus SJ, Rajkumar SV, Weiss M, Stewart AK, Stadtmauer EA, Callander NS, Dreosti LM, Lacy MQ, Fonseca R. Randomized phase III trial of consolidation therapy with bortezomib-lenalidomide-Dexamethasone (VRd) vs bortezomib-dexamethasone (Vd) for patients with multiple myeloma who have completed a dexamethasone based induction regimen. Blood Cancer J. 2016 Jul 29;6(7):e448. [https://doi.org/10.1038/bcj.2016.55 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030380/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27471864/ PubMed] [https://clinicaltrials.gov/study/NCT00522392 NCT00522392] |
− | # '''IFM 2009:''' Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. [https://www. | + | # '''IFM 2009:''' Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. [https://doi.org/10.1056/NEJMoa1611750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28379796/ PubMed] [https://clinicaltrials.gov/study/NCT01191060 NCT01191060] |
− | + | # '''EMN02/HOVON-95:''' Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. [https://doi.org/10.1016/s2352-3026(20)30099-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32359506/ PubMed] [https://clinicaltrials.gov/study/NCT01208766 NCT01208766] | |
+ | ## '''Update:''' Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. [https://doi.org/10.1200/jco.21.01045 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34520219/ PubMed] | ||
+ | #'''DETERMINATION:''' Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2204925 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040899/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35660812/ PubMed] [https://clinicaltrials.gov/study/NCT01208662 NCT01208662] | ||
==Tandem melphalan, then auto HSCT {{#subobject:dd75e9|Regimen=1}}== | ==Tandem melphalan, then auto HSCT {{#subobject:dd75e9|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Protocol variant #1, MEL100 x 2 {{#subobject:b2cefd|Variant=1}}=== | ===Protocol variant #1, MEL100 x 2 {{#subobject:b2cefd|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
− | !style="width: | + | !style="width: 25%"|Study |
− | !style="width: | + | !style="width: 25%"|Dates of enrollment |
− | !style="width: | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2009.22.7561 Palumbo et al. 2010] |
− | |style="background-color:#91cf61"|Phase | + | |2005-2007 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|VGPR or better: 82% | |VGPR or better: 82% | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *[[Multiple_myeloma,_induction#PAD_.28Pegylated_liposomal_doxorubicin_substituted.29|PAD doxil]] induction x 4 |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | |||
− | |||
− | ====Chemotherapy | ||
*[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once (day not specified) | *[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once (day not specified) | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''Two courses''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[# | + | *[[#Lenalidomide_.26_Prednisone_.28RP.29_2|RP]] maintenance |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol variant #2, MEL140, then MEL200 {{#subobject:509dbc|Variant=1}}=== | ===Protocol variant #2, MEL140, then MEL200 {{#subobject:509dbc|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2006-05-022962 Attal et al. 2006 (IFM 99-02)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2000-2003 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma_-_historical#VAD|VAD]] x 3 to 4 | + | *[[Multiple_myeloma_-_historical#VAD|VAD]] induction x 3 to 4 |
− | ====Chemotherapy | + | </div> |
− | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once (day not specified) | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | + | *[[Melphalan (Alkeran)]] as follows: | |
− | + | **First transplant: 140 mg/m<sup>2</sup> IV once (day not specified) | |
− | ==== | + | **Second transplant: 200 mg/m<sup>2</sup> IV once (day not specified) |
− | *[[ | + | ====Supportive therapy==== |
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Multiple_myeloma_-_null_regimens#Observation|Observation]] versus [[#Thalidomide_monotherapy|thalidomide | + | *[[Multiple_myeloma_-_null_regimens#Observation|Observation]] versus [[#Thalidomide_monotherapy|thalidomide]] maintenance |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol variant #3, MEL200 x 2 {{#subobject:dd954b|Variant=1}}=== | ===Protocol variant #3, MEL200 x 2 {{#subobject:dd954b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/bjh.13994 Mai et al. 2016 (GMMG-HD2)] |
|1998-2002 | |1998-2002 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[# | + | |[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan, then auto HSCT]] |
− | |style="background-color:#eeee01"|Non-inferior | + | |style="background-color:#eeee01"|Non-inferior EFS24 (primary endpoint) |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2009-05-222539 Lokhorst et al. 2009 (HOVON-50)] |
|2001-2005 | |2001-2005 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2009-09-241737 Palumbo et al. 2009 (GIS MM2001)] |
|2001-2006 | |2001-2006 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |MEL100 x 2 | + | |[[#Melphalan_monotherapy.2C_then_auto HSCT|MEL100, then auto HSCT]] x 2 |
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611089/ Krishnan et al. 2011 (BMT CTN 0102)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611089/ Krishnan et al. 2011 (BMT CTN 0102)] | ||
|2003-2007 | |2003-2007 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#Melphalan_monotherapy.2C_then_auto HSCT.2C_then_RIC_allo HSCT|MEL200, then auto HSCT, then RIC allo HSCT]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS36 | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS36 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (GMMG-HD4)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1402888 Palumbo et al. 2014 (MPRvsMEL200)] |
|2007-2009 | |2007-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[#MPR|MPR | + | |[[#MPR|MPR]] consolidation |
− | |style="background-color:# | + | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 43 vs 22.4 mo<br>(HR 0.44, 95% CI 0.32-0.61)<br><br>Superior OS (secondary endpoint)<br>OS48: 81.6% vs 65.3%<br>(HR 0.55, 95% CI 0.32-0.93) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(15)00389-7 Gay et al. 2015 (EMN-441)] |
|2009-2011 | |2009-2011 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | | | + | |[[#CRd_888|CRd]] consolidation |
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 43.3 vs 28.6 mo<br>(HR 0.40, 95% CI 0.25-0.625) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *HOVON-50: Induction [[Multiple_myeloma,_induction#TAD|TAD]] x 3 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 | |
− | + | *GMMG-HD4: Induction [[Multiple_myeloma,_induction#PAD|PAD]] x 3 versus [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 | |
− | + | *MPRvsMEL200 & EMN-441: Induction [[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] x 4 | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy | ||
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2 | *[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
− | + | '''Two courses''' | |
− | ==== | + | </div> |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | |||
− | ''' | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *HOVON-50, if induced with VAD: [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]] maintenance | |
− | + | *HOVON-50, if induced with TAD: [[#Thalidomide_monotherapy|Thalidomide]] maintenance | |
− | + | *BMT CTN 0102: [[Multiple_myeloma_-_null_regimens#Observation|No further treatment]] versus [[#Thalidomide_.26_Dexamethasone_.28TD.29_2|Thal-Dex]] maintenance x 1 y | |
− | + | *GMMG-HD4, if induced with PAD: [[#Bortezomib_monotherapy_2|Bortezomib]] maintenance x 2 y | |
− | + | *GMMG-HD4, if induced with VAD: [[#Thalidomide_monotherapy|Thalidomide]] maintenance x 2 y | |
− | + | *MPRvsMEL200: [[#Lenalidomide_monotherapy|Lenalidomide]] maintenance versus [[Multiple_myeloma_-_null_regimens#Observation|no further treatment]] | |
− | + | *EMN-441: [[#Lenalidomide_monotherapy|Lenalidomide]] versus [[#Lenalidomide_.26_Prednisone_.28RP.29_2|RP]] maintenance | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===Protocol variant #4, MEL200 x 2 (split doses) {{#subobject:9ceef8|Variant=1}}=== | ===Protocol variant #4, MEL200 x 2 (split doses) {{#subobject:9ceef8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.V89.3.789 Barlogie et al. 1997 (Total Therapy 1)] |
|1990-1994 | |1990-1994 | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
Line 810: | Line 1,000: | ||
|CR rate: 40% | |CR rate: 40% | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa065464 Bruno et al. 2007] |
|1998-2004 | |1998-2004 | ||
− | |style="background-color:#1a9851"| | + | |style="background-color:#1a9851"|Pseudo-Mendelian randomization<sup>1</sup> |
− | |TBI, then allo HSCT | + | |[[Multiple_myeloma_-_historical#Melphalan_monotherapy.2C_then_auto_HSCT.2C_then_TBI.2C_then_allo_HSCT|MEL-auto HSCT x 1, then TBI, then allo HSCT]] |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Randomization was based on the availability of an HLA-identical sibling.''<br> | ||
''Note: reported efficacy for Total Therapy 1 is based on the 1999 update. Bruno et al. 2007 does not contain treatment details.'' | ''Note: reported efficacy for Total Therapy 1 is based on the 1999 update. Bruno et al. 2007 does not contain treatment details.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma_-_historical# | + | *Induction [[Multiple_myeloma_-_historical#DECA|EDAP]] x 1 |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | |||
− | ====Chemotherapy | ||
*[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once per day on days -3 & -2 | *[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once per day on days -3 & -2 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''Two courses''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa | + | *[[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]] maintenance |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''Total Therapy 1:''' Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997 Feb 1;89(3):789-93. [ | + | # '''Total Therapy 1:''' Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997 Feb 1;89(3):789-93. [https://doi.org/10.1182/blood.V89.3.789 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9028309/ PubMed] |
− | ## '''Update:''' Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999 Jan 1;93(1):55-65. [ | + | ## '''Update:''' Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999 Jan 1;93(1):55-65. [https://doi.org/10.1182/blood.V93.1.55 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9864146/ PubMed] |
− | ## '''Pooled update:''' Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. [ | + | ## '''Pooled update:''' Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. [https://doi.org/10.1200/jco.2009.25.6081 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834471/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20085933/ PubMed] |
− | # '''IFM 99-02:''' Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T; IFM. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15;108(10):3289-94. Epub 2006 Jul 27. [ | + | # '''IFM 99-02:''' Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T; IFM. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15;108(10):3289-94. Epub 2006 Jul 27. [https://doi.org/10.1182/blood-2006-05-022962 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16873668/ PubMed] [https://clinicaltrials.gov/study/NCT00222053 NCT00222053] |
− | ## ''' | + | ## '''Pooled update:''' Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. [https://doi.org/10.1200/jco.2009.25.6081 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834471/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20085933/ PubMed] |
− | # Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedè P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007 Mar 15;356(11):1110-20. [https:// | + | # Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedè P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007 Mar 15;356(11):1110-20. [https://doi.org/10.1056/NEJMoa065464 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/17360989/ PubMed] [https://clinicaltrials.gov/study/NCT00415987 NCT00415987] |
<!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. --> | <!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. --> | ||
− | # '''HOVON-50:''' Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [ | + | # '''HOVON-50:''' Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [https://doi.org/10.1182/blood-2009-05-222539 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19880501/ PubMed] [https://clinicaltrials.gov/study/NCT00028886 NCT00028886] |
− | ## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https:// | + | ## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905/ PubMed] |
− | # '''GIS MM2001:''' Palumbo A, Bringhen S, Bruno B, Falcone AP, Liberati AM, Grasso M, Ria R, Pisani F, Cangialosi C, Caravita T, Levi A, Meloni G, Nozza A, Pregno P, Gabbas A, Callea V, Rizzo M, Annino L, De Stefano V, Musto P, Baldi I, Cavallo F, Petrucci MT, Massaia M, Boccadoro M. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010 Mar 11;115(10):1873-9. Epub 2009 Dec 1. Erratum in: Blood. 2010 Sep 23;116(12):2195. [ | + | # '''GIS MM2001:''' Palumbo A, Bringhen S, Bruno B, Falcone AP, Liberati AM, Grasso M, Ria R, Pisani F, Cangialosi C, Caravita T, Levi A, Meloni G, Nozza A, Pregno P, Gabbas A, Callea V, Rizzo M, Annino L, De Stefano V, Musto P, Baldi I, Cavallo F, Petrucci MT, Massaia M, Boccadoro M. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010 Mar 11;115(10):1873-9. Epub 2009 Dec 1. Erratum in: Blood. 2010 Sep 23;116(12):2195. [https://doi.org/10.1182/blood-2009-09-241737 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19965659/ PubMed] [https://clinicaltrials.gov/study/NCT00950768 NCT00950768] |
− | + | # Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [https://doi.org/10.1200/jco.2009.22.7561 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20048187/ PubMed] EudraCT 2005-004714-32 | |
− | ## '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [ | + | ## '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [https://doi.org/10.1182/blood-2013-02-483073 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23775712/ PubMed] |
− | # '''GIMEMA MM-BO2005:''' Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. [https:// | + | # '''GIMEMA MM-BO2005:''' Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. [https://doi.org/10.1016/s0140-6736(10)61424-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21146205/ PubMed] [https://clinicaltrials.gov/study/NCT01134484 NCT01134484] |
− | ## '''Update:''' Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. [ | + | ## '''Update:''' Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. [https://doi.org/10.1182/blood-2012-02-408898 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22498745/ PubMed] |
− | # '''BMT CTN 0102:''' Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; BMT CTN. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. Epub 2011 Sep 29. [https:// | + | # '''BMT CTN 0102:''' Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; BMT CTN. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. Epub 2011 Sep 29. [https://doi.org/10.1016/s1470-2045(11)70243-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611089/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21962393/ PubMed] [https://clinicaltrials.gov/study/NCT00075829 NCT00075829] |
− | + | # '''GMMG-HD4:''' Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. [https://doi.org/10.1200/jco.2011.39.6820 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22802322/ PubMed] ISRCTN64455289 | |
− | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [ | + | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [https://doi.org/10.1182/blood-2011-09-379164 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22160383/ PubMed] |
− | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https:// | + | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https://doi.org/10.1038/leu.2017.211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28761118/ PubMed] |
− | # '''Meta-analysis:''' Armeson KE, Hill EG, Costa LJ. Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment. Bone Marrow Transplant. 2013 Apr;48(4):562-7. Epub 2012 Sep 10. Review. [https://doi.org/10.1038/bmt.2012.173 link to original article] [https:// | + | # '''Meta-analysis:''' Armeson KE, Hill EG, Costa LJ. Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment. Bone Marrow Transplant. 2013 Apr;48(4):562-7. Epub 2012 Sep 10. Review. [https://doi.org/10.1038/bmt.2012.173 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975377/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22964593/ PubMed] |
− | # '''MPRvsMEL200:''' Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. [https:// | + | # '''MPRvsMEL200:''' Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. [https://doi.org/10.1056/NEJMoa1402888 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25184862/ PubMed] [https://clinicaltrials.gov/study/NCT00551928 NCT00551928] |
− | # '''EMN-441:''' Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. [https:// | + | # '''EMN-441:''' Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. [https://doi.org/10.1016/S1470-2045(15)00389-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26596670/ PubMed] [https://clinicaltrials.gov/study/NCT01091831 NCT01091831] |
− | + | # '''GMMG-HD2:''' Mai EK, Benner A, Bertsch U, Brossart P, Hänel A, Kunzmann V, Naumann R, Neben K, Egerer G, Ho AD, Hillengass J, Raab MS, Neubauer A, Peyn A, Ko YD, Peter N, Scheid C, Goldschmidt H. Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial. Br J Haematol. 2016 Jun;173(5):731-41. Epub 2016 Mar 17. [https://doi.org/10.1111/bjh.13994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26990892/ PubMed] DRKS00008864 | |
+ | # '''EMN02/HOVON-95:''' Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. [https://doi.org/10.1016/s2352-3026(20)30099-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32359506/ PubMed] [https://clinicaltrials.gov/study/NCT01208766 NCT01208766] | ||
+ | ## '''Update:''' Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. [https://doi.org/10.1200/jco.21.01045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34520219/ PubMed] | ||
+ | #'''DSMM V:''' [https://clinicaltrials.gov/study/NCT00546988 NCT00546988] | ||
==Thalidomide & Dexamethasone (TD) {{#subobject:13b509|Regimen=1}}== | ==Thalidomide & Dexamethasone (TD) {{#subobject:13b509|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TD: '''<u>T</u>'''halidomide & '''<u>D</u>'''examethasone | TD: '''<u>T</u>'''halidomide & '''<u>D</u>'''examethasone | ||
<br>Thal-Dex: '''<u>Thal</u>'''idomide & '''<u>Dex</u>'''amethasone | <br>Thal-Dex: '''<u>Thal</u>'''idomide & '''<u>Dex</u>'''amethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:f79d0|Variant=1}}=== | ===Regimen {{#subobject:f79d0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s0140-6736(10)61424-9 Cavo et al. 2010 (GIMEMA MM-BO2005)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2006-2008 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem MEL200 with auto HSCT]], with interim Thal-Dex maintenance (see paper for details) | + | *[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem MEL200 with auto HSCT]] consolidation, with interim [[#Thalidomide_.26_Dexamethasone_.28TD.29|Thal-Dex]] maintenance (see paper for details) |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Thalidomide (Thalomid)]] 100 mg PO once per day | + | *[[Thalidomide (Thalomid)]] 100 mg PO once per day |
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 20 to 23 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 20 to 23 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Acyclovir (Zovirax)]] prophylaxis recommended | *[[Acyclovir (Zovirax)]] prophylaxis recommended | ||
− | |||
'''35-day cycle for 2 cycles''' | '''35-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_2|Dexamethasone | + | *[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_2|Dexamethasone]] maintenance |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''GIMEMA MM-BO2005:''' Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. [https:// | + | # '''GIMEMA MM-BO2005:''' Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. [https://doi.org/10.1016/s0140-6736(10)61424-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21146205/ PubMed] [https://clinicaltrials.gov/study/NCT01134484 NCT01134484] |
− | ## '''Update:''' Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. [ | + | ## '''Update:''' Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. [https://doi.org/10.1182/blood-2012-02-408898 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22498745/ PubMed] |
− | + | ==Thalidomide & Prednisolone (TP) {{#subobject:1agdc9|Regimen=1}}== | |
− | ==TP {{#subobject:1agdc9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TP: '''<u>T</u>'''halidomide & '''<u>P</u>'''rednisolone | TP: '''<u>T</u>'''halidomide & '''<u>P</u>'''rednisolone | ||
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:9gubi8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 904: | Line 1,101: | ||
|[https://doi.org/10.1080/10428194.2019.1579322 Horvath et al. 2019 (VCAT)] | |[https://doi.org/10.1080/10428194.2019.1579322 Horvath et al. 2019 (VCAT)] | ||
|2012-2016 | |2012-2016 | ||
− | |style="background-color:#1a9851"| | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |VTP | + | |[[#VTP_999|VTP]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR + VGPR rate | | style="background-color:#ffffbf" |Did not meet primary endpoint of CR + VGPR rate | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VDC|VDC]] x 3, then high-dose auto HSCT | + | *Induction [[Multiple_myeloma,_induction#VDC|VDC]] x 3, then [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|high-dose auto HSCT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Thalidomide (Thalomid)]] 100 mg PO once per day | + | *[[Thalidomide (Thalomid)]] as follows: |
− | *[[Prednisolone (Millipred)]] 50 mg PO once every other day | + | **Cycles 1 to 13: 100 mg PO once per day on days 1 to 28 |
− | + | ====Glucocorticoid therapy==== | |
+ | *[[Prednisolone (Millipred)]] 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''VCAT:''' Horvath N, Spencer A, Kenealy M, Joshua D, Campbell PJ, Lee JJ, Hou J, Qiu L, Kalff A, Khong T, Londhe A, Siggins S, van Kooten Losio M, Eisbacher M, Prince HM. Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study. Leuk Lymphoma. 2019 Sep;60(9):2122-2133. Epub 2019 Feb 19. [https://doi.org/10.1080/10428194.2019.1579322 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30777794 PubMed] NCT01539083 | + | # '''VCAT:''' Horvath N, Spencer A, Kenealy M, Joshua D, Campbell PJ, Lee JJ, Hou J, Qiu L, Kalff A, Khong T, Londhe A, Siggins S, van Kooten Losio M, Eisbacher M, Prince HM. Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study. Leuk Lymphoma. 2019 Sep;60(9):2122-2133. Epub 2019 Feb 19. [https://doi.org/10.1080/10428194.2019.1579322 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30777794/ PubMed] [https://clinicaltrials.gov/study/NCT01539083 NCT01539083] |
==VMP {{#subobject:028a65|Regimen=1}}== | ==VMP {{#subobject:028a65|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
VMP: '''<u>V</u>'''elcade (Bortezomib), '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone | VMP: '''<u>V</u>'''elcade (Bortezomib), '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a9c980|Variant=1}}=== | ===Regimen {{#subobject:a9c980|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2006-04-019778 Mateos et al. 2006] |
− | |style="background-color:#91cf61"|Phase | + | |2004-2005 |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
''Note: this was the phase II portion of this phase I/II study.'' | ''Note: this was the phase II portion of this phase I/II study.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VMP|VMP | + | *[[Multiple_myeloma,_induction#VMP|VMP]] induction |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 9 mg/m<sup>2</sup> PO once per day on days 1 to 4 | *[[Melphalan (Alkeran)]] 9 mg/m<sup>2</sup> PO once per day on days 1 to 4 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 4 | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 4 | ||
− | |||
'''35-day cycle for 5 cycles''' | '''35-day cycle for 5 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, Díaz-Mediavilla J, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, de Arriba F, Alegre A, Oriol A, Carrera D, García-Laraña J, García-Sanz R, Bladé J, Prósper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006 Oct 1;108(7):2165-72. Epub 2006 Jun 13. [ | + | # Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, Díaz-Mediavilla J, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, de Arriba F, Alegre A, Oriol A, Carrera D, García-Laraña J, García-Sanz R, Bladé J, Prósper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006 Oct 1;108(7):2165-72. Epub 2006 Jun 13. [https://doi.org/10.1182/blood-2006-04-019778 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16772605/ PubMed] |
− | + | # '''EMN02/HOVON-95:''' Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. [https://doi.org/10.1016/s2352-3026(20)30099-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32359506/ PubMed] [https://clinicaltrials.gov/study/NCT01208766 NCT01208766] | |
+ | ## '''Update:''' Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. [https://doi.org/10.1200/jco.21.01045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34520219/ PubMed] | ||
==VTD {{#subobject:c74cc6|Regimen=1}}== | ==VTD {{#subobject:c74cc6|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
VTD: '''<u>V</u>'''elcade (Bortezomib), '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone | VTD: '''<u>V</u>'''elcade (Bortezomib), '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, "vTD" {{#subobject:ac81d8|Variant=1}}=== | ===Regimen variant #1, "vTD" {{#subobject:ac81d8|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943328/ Lok et al. 2014] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943328/ Lok et al. 2014] | ||
+ | |2011-2013 | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan with autologous hematopoietic stem cell transplantation]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11 | ||
− | *[[Thalidomide (Thalomid)]] 100 mg PO once per day | + | *[[Thalidomide (Thalomid)]] 100 mg PO once per day |
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg (route not specified) once per day on days 1 to 4 | *[[Dexamethasone (Decadron)]] 40 mg (route not specified) once per day on days 1 to 4 | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:85c53d|Variant=1}}=== | ===Regimen variant #2 {{#subobject:85c53d|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s0140-6736(10)61424-9 Cavo et al. 2010 (GIMEMA MM-BO2005)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2006-2008 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
''VTD consolidation is to begin 3 months after the second transplant.'' | ''VTD consolidation is to begin 3 months after the second transplant.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VTD|VTD | + | *[[Multiple_myeloma,_induction#VTD|VTD]] induction, then [[#Melphalan_monotherapy.2C_then_auto_HSCT|high-dose melphalan with tandem autologous hematopoietic stem cell transplant]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 35 | *[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 35 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Acyclovir (Zovirax)]] prophylaxis recommended | *[[Acyclovir (Zovirax)]] prophylaxis recommended | ||
− | |||
'''35-day cycle for 2 cycles''' | '''35-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_2|Dexamethasone | + | *[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_2|Dexamethasone]] maintenance |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3 {{#subobject:9a493a|Variant=1}}=== | ===Regimen variant #3 {{#subobject:9a493a|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2009.23.7172 Ladetto et al. 2010 (GIMEMA VEL-03-096)] |
− | |style="background-color:#91cf61"|Phase | + | |2004-08 to 2007-07 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan, then HSCT]] consolidation, with at least a very good partial response (VGPR) |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day, increased by 50 mg each week, up to a maximum of 200 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day, increased by 50 mg each week, up to a maximum of 200 mg PO once per day | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18 | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18 | ||
− | |||
'''35-day cycle for 4 cycles''' | '''35-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''GIMEMA VEL-03-096:''' Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, Crippa C, De Rosa L, Pregno P, Grasso M, Liberati AM, Caravita T, Pisani F, Guglielmelli T, Callea V, Musto P, Cangialosi C, Passera R, Boccadoro M, Palumbo A. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010 Apr 20;28(12):2077-84. Epub 2010 Mar 22. [ | + | # '''GIMEMA VEL-03-096:''' Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, Crippa C, De Rosa L, Pregno P, Grasso M, Liberati AM, Caravita T, Pisani F, Guglielmelli T, Callea V, Musto P, Cangialosi C, Passera R, Boccadoro M, Palumbo A. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010 Apr 20;28(12):2077-84. Epub 2010 Mar 22. [https://doi.org/10.1200/jco.2009.23.7172 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20308672/ PubMed] EudraCT 2004-000531-28 |
− | ## '''Update:''' Ferrero S, Ladetto M, Drandi D, Cavallo F, Genuardi E, Urbano M, Caltagirone S, Grasso M, Rossini F, Guglielmelli T, Cangialosi C, Liberati AM, Callea V, | + | ## '''Update:''' Ferrero S, Ladetto M, Drandi D, Cavallo F, Genuardi E, Urbano M, Caltagirone S, Grasso M, Rossini F, Guglielmelli T, Cangialosi C, Liberati AM, Callea V, Caravita T, Crippa C, De Rosa L, Pisani F, Falcone AP, Pregno P, Oliva S, Terragna C, Musto P, Passera R, Boccadoro M, Palumbo A. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival. Leukemia. 2015 Mar;29(3):689-95. Epub 2014 Jul 16. [https://doi.org/10.1038/leu.2014.219 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25027515/ PubMed] |
− | # '''GIMEMA MM-BO2005:''' Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. [https:// | + | # '''GIMEMA MM-BO2005:''' Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. [https://doi.org/10.1016/s0140-6736(10)61424-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21146205/ PubMed] [https://clinicaltrials.gov/study/NCT01134484 NCT01134484] |
− | ## '''Update:''' Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. [ | + | ## '''Update:''' Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. [https://doi.org/10.1182/blood-2012-02-408898 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22498745/ PubMed] |
− | # Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous bortezomib incorporated into the bortezomib-thalidomide-dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. [ | + | # Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous bortezomib incorporated into the bortezomib-thalidomide-dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. [https://doi.org/10.3324/haematol.2013.100396 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943328/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24532044/ PubMed] |
=Maintenance after first-line therapy= | =Maintenance after first-line therapy= | ||
''Note that there is no crisp distinction between consolidation and maintenance. Generally regimens that are intended for a long or indefinite duration would be considered maintenance, whereas regimens with a short intended course would be considered consolidation.'' | ''Note that there is no crisp distinction between consolidation and maintenance. Generally regimens that are intended for a long or indefinite duration would be considered maintenance, whereas regimens with a short intended course would be considered consolidation.'' | ||
− | |||
==Bortezomib monotherapy {{#subobject:d759b6|Regimen=1}}== | ==Bortezomib monotherapy {{#subobject:d759b6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, IV x 2 years {{#subobject:85e781|Variant=1}}=== | ===Regimen variant #1, IV x 2 years {{#subobject:85e781|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (HOVON-65)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) |
|[[#Thalidomide_monotherapy|Thalidomide]] | |[[#Thalidomide_monotherapy|Thalidomide]] | ||
− | |style="background-color:#1a9850"|Superior PFS ( | + | |style="background-color:#1a9850"|Superior PFS<sup>1</sup> (primary endpoint) |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (GMMG-HD4)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) |
|[[#Thalidomide_monotherapy|Thalidomide]] | |[[#Thalidomide_monotherapy|Thalidomide]] | ||
− | |style="background-color:#1a9850"|Superior PFS ( | + | |style="background-color:#1a9850"|Superior PFS<sup>1</sup> (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>In the initial publication, this arm seemed to have an overall survival advantage; this was no longer present in the updated report of 2017. HOVON-65/GMMG-HD4 was a single phase 3 RCT but the consolidation was different by group, so is reported here as 2 distinct trials.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *HOVON-65: [[# | + | *HOVON-65: [[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with single autologous hematopoietic stem cell transplant]] consolidation |
− | *GMMG-HD4: [[#Tandem_melphalan.2C_then_auto_HSCT|High-dose melphalan with tandem autologous hematopoietic stem cell transplants]] | + | *GMMG-HD4: [[#Tandem_melphalan.2C_then_auto_HSCT|High-dose melphalan with tandem autologous hematopoietic stem cell transplants]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once on day 1 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''14-day cycle for 52 cycles (2 years)''' | '''14-day cycle for 52 cycles (2 years)''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, SC, indefinite {{#subobject:3897c8|Variant=1}}=== | ===Regimen variant #2, SC, indefinite {{#subobject:3897c8|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1038/leu.2016.36 Larocca et al. 2016 (MMY2069)] | |[https://doi.org/10.1038/leu.2016.36 Larocca et al. 2016 (MMY2069)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2010-10 to 2012-08 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *Induction [[Multiple_myeloma,_induction#Bortezomib_.26_Prednisone_.28VP.29|VP]] x 9 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once on day 1 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''HOVON-65 | + | # '''HOVON-65:''' Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. [https://doi.org/10.1200/jco.2011.39.6820 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22802322/ PubMed] ISRCTN64455289 |
− | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [ | + | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [https://doi.org/10.1182/blood-2011-09-379164 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22160383/ PubMed] |
− | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https:// | + | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https://doi.org/10.1038/leu.2017.211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28761118/ PubMed] |
− | # '''MMY2069:''' Larocca A, Bringhen S, Petrucci MT, Oliva S, Falcone AP, Caravita T, Villani O, Benevolo G, Liberati AM, Morabito F, Montefusco V, Passera R, De Rosa L, Omedé P, Vincelli ID, Spada S, Carella AM, Ponticelli E, Derudas D, Genuardi M, Guglielmelli T, Nozzoli C, Aghemo E, De Paoli L, Conticello C, Musolino C, Offidani M, Boccadoro M, Sonneveld P, Palumbo A. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. Leukemia. 2016 Jun;30(6):1320-6. [https://doi.org/10.1038/leu.2016.36 link to original article] ''' | + | # '''GMMG-HD4:''' Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. [https://doi.org/10.1200/jco.2011.39.6820 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22802322/ PubMed] ISRCTN64455289 |
− | + | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [https://doi.org/10.1182/blood-2011-09-379164 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22160383/ PubMed] | |
− | == | + | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https://doi.org/10.1038/leu.2017.211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28761118/ PubMed] |
− | {| class="wikitable" style=" | + | # '''MMY2069:''' Larocca A, Bringhen S, Petrucci MT, Oliva S, Falcone AP, Caravita T, Villani O, Benevolo G, Liberati AM, Morabito F, Montefusco V, Passera R, De Rosa L, Omedé P, Vincelli ID, Spada S, Carella AM, Ponticelli E, Derudas D, Genuardi M, Guglielmelli T, Nozzoli C, Aghemo E, De Paoli L, Conticello C, Musolino C, Offidani M, Boccadoro M, Sonneveld P, Palumbo A. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. Leukemia. 2016 Jun;30(6):1320-6. Epub 2016 Feb 22. [https://doi.org/10.1038/leu.2016.36 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26898189/ PubMed] [https://clinicaltrials.gov/study/NCT01190787 NCT01190787] |
+ | ==Bortezomib & Dexamethasone (Vd) {{#subobject:f25dc6|Regimen=1}}== | ||
+ | VD: '''<u>V</u>'''elcade (Bortezomib) & low-dose '''<u>d</u>'''examethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:8ce3fb|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1111/bjh.14536 Berdeja et al. 2017 (SCRI MM 23)] | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |ORR: 91% | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''Note: this is the modified treatment schema.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Induction [[Multiple_myeloma,_induction#BBD|BBD]] x 8 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV or SC once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once on day 1 | ||
+ | '''14-day cycle for 52 cycles (2 years)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SCRI MM 23:''' Berdeja JG, Bauer T, Arrowsmith E, Essell J, Murphy P, Reeves JA Jr, Boccia RV, Donnellan W, Flinn I. Phase II study of bendamustine, bortezomib and dexamethasone (BBD) in the first-line treatment of patients with multiple myeloma who are not candidates for high dose chemotherapy. Br J Haematol. 2017 Apr;177(2):254-262. Epub 2017 Feb 7. [https://doi.org/10.1111/bjh.14536 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28169430/ PubMed] [https://clinicaltrials.gov/study/NCT01056276 NCT01056276] | ||
+ | ==Carfilzomib monotherapy {{#subobject:cf0af4|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, bi-weekly {{#subobject:fdc86d|Variant=1}}=== | ===Regimen variant #1, bi-weekly {{#subobject:fdc86d|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2014-03-563759 Bringhen et al. 2014 (IST-CAR-506)] |
− | |style="background-color:#91cf61"|Phase | + | |2011-06-21 to 2012-09-15 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *Induction [[Multiple_myeloma,_induction#KCD|CCyd]] x 9 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 2, 15, 16 | *[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 2, 15, 16 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, weekly {{#subobject:54dd57|Variant=1}}=== | ===Regimen variant #2, weekly {{#subobject:54dd57|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1038/leu.2017.327 Bringhen et al. 2017 (IST-CAR-561)] |
− | |style="background-color:#91cf61"|Phase | + | |2013-04-10 to 2015-08-24 |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
− | ''Note: this | + | ''Note: this was the MTD established for the phase 2 portion of the trial.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *Induction [[Multiple_myeloma,_induction#KCD|wKCyd]] x 9 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Carfilzomib (Kyprolis)]] 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Carfilzomib (Kyprolis)]] 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- # '''Abstract:''' Palumbo, Antonio; Bringhen, Sara; Villani, Oreste; Siniscalchi, Agostina; Russo, Eleonora; Uccello, Giuseppina; Cerrato, Chiara; Gilestro, Milena; Rossi, Davide; Boccadoro, Mario. Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) for Newly Diagnosed Multiple Myeloma (MM) Patients. ASH Annual Meeting Abstracts 2012 120: 730 [https://doi.org/10.1182/blood.V120.21.730.730 link to abstract] --> | ||
+ | # '''IST-CAR-506:''' Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omedé P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. Epub 2014 May 22. [https://doi.org/10.1182/blood-2014-03-563759 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24855212/ PubMed] [https://clinicaltrials.gov/study/NCT01346787 NCT01346787] | ||
+ | # '''IST-CAR-561:''' Bringhen S, D'Agostino M, De Paoli L, Montefusco V, Liberati AM, Galieni P, Grammatico S, Muccio VE, Esma F, De Angelis C, Musto P, Ballanti S, Offidani M, Petrucci MT, Gaidano G, Corradini P, Palumbo A, Sonneveld P, Boccadoro M. Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. Leukemia. 2018 Apr;32(4):979-985. Epub 2017 Nov 16. [https://doi.org/10.1038/leu.2017.327 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29263440/ PubMed] [https://clinicaltrials.gov/study/NCT01857115 NCT01857115] | ||
+ | ==Carfilzomib & Lenalidomide (KR) {{#subobject:chacv4|Regimen=1}}== | ||
+ | KR: '''<u>K</u>'''yprolis (Carfilzomib) & '''<u>R</u>'''evlimid (Lenalidomide) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:fdab1d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(21)00535-0 Gay et al. 2021 (FORTE)] | ||
+ | |2015-2017 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | ||
+ | |[[#Lenalidomide_monotherapy|Lenalidomide]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (co-primary endpoint)<br>PFS36: 75% vs 65%<br>(HR 0.64, 95% CI 0.44-0.94) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: treatment details are as provided in a 2020 ASH abstract.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Carfilzomib (Kyprolis)]] as follows: | ||
+ | **Cycles 1 up to 26: 70 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
+ | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''FORTE:''' Gay F, Musto P, Rota-Scalabrini D, Bertamini L, Belotti A, Galli M, Offidani M, Zamagni E, Ledda A, Grasso M, Ballanti S, Spadano A, Cea M, Patriarca F, D'Agostino M, Capra A, Giuliani N, de Fabritiis P, Aquino S, Palmas A, Gamberi B, Zambello R, Petrucci MT, Corradini P, Cavo M, Boccadoro M. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. Lancet Oncol. 2021 Dec;22(12):1705-1720. Epub 2021 Nov 11. [https://doi.org/10.1016/s1470-2045(21)00535-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34774221/ PubMed] [https://clinicaltrials.gov/study/NCT02203643 NCT02203643] | |
− | |||
− | |||
==Daratumumab monotherapy {{#subobject:744fd9|Regimen=1}}== | ==Daratumumab monotherapy {{#subobject:744fd9|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, q4wk indefinite {{#subobject:9dcf90|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa1714678 Mateos et al. 2017 (ALCYONE)] | ||
+ | |2015-02-09 to 2016-07-14 | ||
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | {| class="wikitable" style="width: | + | ====Preceding treatment==== |
− | !style="width: | + | *Induction [[Multiple_myeloma,_induction#Dara-VMP|Dara-VMP]] x 9 |
− | !style="width: | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Daratumumab (Darzalex)]] 16 mg/kg IV once on day 1 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg IV or PO once on day 1, prior to daratumumab | ||
+ | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
+ | ===Regimen variant #2, q8wk x 2y {{#subobject:9dgc91|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(19)31240-1 Moreau et al. 2019 (CASSIOPEIA part 2)] |
− | |style="background-color:# | + | |2016-2018 |
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (co-primary endpoint)<br>Median PFS: NYR vs 46.7 mo<br>(HR 0.53, 95% CI 0.42-0.68) | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: the protocol is somewhat confusing about what dose of steroids to use as premedication. See the original paper.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[ | + | *[[#Dara-VTD|Data-VTD]] versus [[#VTD|VTD]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Daratumumab (Darzalex)]] 16 mg/kg IV once on day 1 | *[[Daratumumab (Darzalex)]] 16 mg/kg IV once on day 1 | ||
− | + | '''56-day cycle for 13 cycles (2 years)''' | |
− | + | </div></div> | |
− | |||
− | |||
− | ''' | ||
===References=== | ===References=== | ||
− | # '''ALCYONE:''' Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. Epub 2017 Dec 12. [https:// | + | # '''ALCYONE:''' Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. Epub 2017 Dec 12. [https://doi.org/10.1056/NEJMoa1714678 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29231133/ PubMed] [https://clinicaltrials.gov/study/NCT02195479 NCT02195479] |
+ | # '''CASSIOPEIA part 2:''' Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, Béné MC, Zweegman S, Caillon H, Caillot D, Corre J, Delforge M, Dejoie T, Doyen C, Facon T, Sonntag C, Fontan J, Mohty M, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Macro M, Orsini-Piocelle F, Roussel M, Stoppa AM, van de Donk NWCJ, Wuillème S, Broijl A, Touzeau C, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Offner F, Escoffre-Barbe M, Eveillard JR, Garidi R, Ahmadi T, Krevvata M, Zhang K, de Boer C, Vara S, Kampfenkel T, Vanquickelberghe V, Vermeulen J, Avet-Loiseau H, Sonneveld P. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1378-1390. Epub 2021 Sep 13. [https://doi.org/10.1016/s1470-2045(21)00428-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34529931/ PubMed] [https://clinicaltrials.gov/study/NCT02541383 NCT02541383] | ||
==Ixazomib monotherapy {{#subobject:af8692|Regimen=1}}== | ==Ixazomib monotherapy {{#subobject:af8692|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, indefinite {{#subobject:214582|Variant=1}}=== | ===Regimen variant #1, indefinite {{#subobject:214582|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)71125-8 Kumar et al. 2014 (C16005)] |
− | |style="background-color:#91cf61"|Phase | + | |2010-2012 |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#IRd|IRd]] x 12 | + | *Induction [[Multiple_myeloma,_induction#IRd|IRd]] x 12 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Ixazomib (Ninlaro)]] 4 mg PO once per day on days 1, 8, 15 | *[[Ixazomib (Ninlaro)]] 4 mg PO once per day on days 1, 8, 15 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 2-year course {{#subobject:532db5|Variant=1}}=== | ===Regimen variant #2, 2-year course {{#subobject:532db5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(18)33003-4 Dimopoulos et al. 2018 (TOURMALINE-MM3)] |
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Multiple_myeloma_-_historical#Placebo|Placebo]] | |[[Multiple_myeloma_-_historical#Placebo|Placebo]] | ||
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 26.5 vs 21.3 mo<br>(HR 0.72, 95% CI 0.58-0.89) |
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768338/ Dimopoulos et al. 2020 (TOURMALINE-MM4)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Multiple_myeloma_-_historical#Placebo|Placebo]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 17.4 vs 9.4 mo<br>(HR 0.66, 95% CI 0.54-0.80) | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: dose was escalated in cycle 5 if the prior dose was tolerated.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *TOURMALINE-MM3: [[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan with auto HSCT]] consolidation |
+ | *TOURMALINE-MM4: Standard-of-care induction therapy x 6 to 12 months | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Ixazomib (Ninlaro)]] as follows: | *[[Ixazomib (Ninlaro)]] as follows: | ||
**Cycles 1 to 4: 3 mg PO once per day on days 1, 8, 15 | **Cycles 1 to 4: 3 mg PO once per day on days 1, 8, 15 | ||
− | ** | + | **Cycles 5 to 26: 4 mg PO once per day on days 1, 8, 15 |
− | |||
'''28-day cycle for up to 26 cycles (2 years)''' | '''28-day cycle for up to 26 cycles (2 years)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- Presented at ASH 2012 and ASH 2014, Abstract 82: Long-Term Ixazomib Maintenance Is Tolerable and Improves Depth of Response Following Ixazomib-Lenalidomide-Dexamethasone Induction in Patients (Pts) with Previously Untreated Multiple Myeloma (MM): Phase 2 Study Results --> | <!-- Presented at ASH 2012 and ASH 2014, Abstract 82: Long-Term Ixazomib Maintenance Is Tolerable and Improves Depth of Response Following Ixazomib-Lenalidomide-Dexamethasone Induction in Patients (Pts) with Previously Untreated Multiple Myeloma (MM): Phase 2 Study Results --> | ||
− | # '''C16005:''' Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Di Bacco A, Estevam J, Gupta N, Hui AM, Rajkumar V, Richardson PG. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol. 2014 Dec;15(13):1503-12. [https:// | + | # '''C16005:''' Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Di Bacco A, Estevam J, Gupta N, Hui AM, Rajkumar V, Richardson PG. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol. 2014 Dec;15(13):1503-12. Epub 2014 Nov 14. [https://doi.org/10.1016/S1470-2045(14)71125-8 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25456369/ PubMed] [https://clinicaltrials.gov/study/NCT01217957 NCT01217957] |
− | ## '''Update:''' Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Rajkumar SV, Richardson PG. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance. Leukemia. 2019 Jul;33(7):1736-1746. Epub 2019 Jan 29. [https:// | + | ## '''Update:''' Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Rajkumar SV, Richardson PG. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance. Leukemia. 2019 Jul;33(7):1736-1746. Epub 2019 Jan 29. [https://doi.org/10.1038/s41375-019-0384-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6755968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30696949/ PubMed] |
− | # '''TOURMALINE-MM3:''' Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, Goldschmidt H, Maisnar V, Moreau P, Min CK, Pluta A, Chng WJ, Kaiser M, Zweegman S, Mateos MV, Spencer A, Iida S, Morgan G, Suryanarayan K, Teng Z, Skacel T, Palumbo A, Dash AB, Gupta N, Labotka R, Rajkumar SV; TOURMALINE-MM3 study group. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Jan 19;393(10168):253-264. Epub 2018 Dec 10. [https:// | + | # '''TOURMALINE-MM3:''' Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, Goldschmidt H, Maisnar V, Moreau P, Min CK, Pluta A, Chng WJ, Kaiser M, Zweegman S, Mateos MV, Spencer A, Iida S, Morgan G, Suryanarayan K, Teng Z, Skacel T, Palumbo A, Dash AB, Gupta N, Labotka R, Rajkumar SV; TOURMALINE-MM3 study group. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Jan 19;393(10168):253-264. Epub 2018 Dec 10. [https://doi.org/10.1016/S0140-6736(18)33003-4 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30545780/ PubMed] [https://clinicaltrials.gov/study/NCT02181413 NCT02181413] |
− | + | # '''TOURMALINE-MM4:''' Dimopoulos MA, Špička I, Quach H, Oriol A, Hájek R, Garg M, Beksac M, Bringhen S, Katodritou E, Chng WJ, Leleu X, Iida S, Mateos MV, Morgan G, Vorog A, Labotka R, Wang B, Palumbo A, Lonial S; TOURMALINE-MM4 study group. Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol. 2020 Dec 1;38(34):4030-4041. Epub 2020 Oct 6. [https://doi.org/10.1200/jco.20.02060 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768338/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33021870/ PubMed] [https://clinicaltrials.gov/study/NCT02312258 NCT02312258] | |
− | == | + | ==Isa-Rd {{#subobject:9f1904|Regimen=1}}== |
− | {| class="wikitable" style=" | + | Isa-Rd: '''<u>Isa</u>'''tuximab, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:e3fc11v|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2400712 Facon et al. 2024 (IMROZ)] | ||
+ | |2017-12 to 2019-03 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Induction [[Multiple_myeloma,_induction#Isa-RVd|Isa-RVd]] x 4 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Isatuximab (Sarclisa)]] as follows: | ||
+ | **Cycles 1 to 17: 10 mg/kg IV once per day on days 1 & 15 | ||
+ | **Cycle 18 onwards: 10 mg/kg IV once on day 1 | ||
+ | *[[Lenalidomide (Revlimid)]] by the following laboratory-based criteria: | ||
+ | **eGFR 60 mL/min/1.73m<sup>2</sup> or more: 25 mg PO once per day on days 1 to 21 | ||
+ | **eGFR 30 up to 60 mL/min/1.73m<sup>2</sup>: 10 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''IMROZ:''' Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hájek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Brégeault MF, Macé S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Jun 3. Epub ahead of print. [https://doi.org/10.1056/nejmoa2400712 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38832972/ PubMed] [https://clinicaltrials.gov/study/NCT03319667 NCT03319667] | ||
+ | ==KRd {{#subobject:9f1904|Regimen=1}}== | ||
KRd: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | KRd: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | ||
<br>CRd: '''<u>C</u>'''arfilzomib, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | <br>CRd: '''<u>C</u>'''arfilzomib, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | ||
− | ===Regimen {{#subobject:df3763|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1, biweekly carfilzomib {{#subobject:df3763|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162553/ Jakubowiak et al. 2012 (UMCC 2009.056)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162553/ Jakubowiak et al. 2012 (UMCC 2009.056)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2009-2011 |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
− | ''This is the MTD dosing in this phase | + | ''This is the MTD dosing in this phase 1/2 trial.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#KRd|KRd]] x 8 | + | *Induction [[Multiple_myeloma,_induction#KRd|KRd]] x 8 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 2, 15, 16 | *[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 2, 15, 16 | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 20 mg (route not specified) once per day on days 1, 8, 15, 22 | *[[Dexamethasone (Decadron)]] 20 mg (route not specified) once per day on days 1, 8, 15, 22 | ||
− | |||
'''28-day cycle for 16 cycles''' | '''28-day cycle for 16 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *It was recommended that patients proceed to [[#Lenalidomide_monotherapy|lenalidomide maintenance]] | + | *UMCC 2009.056: It was recommended that patients proceed to [[#Lenalidomide_monotherapy|lenalidomide]] maintenance |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, carfilzomib 3 weeks on/1 week off {{#subobject:df3763|Variant=2}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337122/ Dytfeld et al. 2023 (ATLAS-MM)] | ||
+ | |2016-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Lenalidomide_monotherapy|Lenalidomide]] | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 59.1 vs 41.4 mo<br>(HR 0.51, 95% CI 0.31-0.86) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This trial is labeled ATLAS-MM here, to distinguish from trials named ATLAS in multiple other cancer subtypes.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with single autologous hematopoietic stem cell transplant]] consolidation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16 | ||
+ | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycle for 36 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''UMCC 2009.056:''' Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. Epub 2012 Jun 4. [ | + | # '''UMCC 2009.056:''' Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. Epub 2012 Jun 4. [https://doi.org/10.1182/blood-2012-04-422683 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162553/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22665938/ PubMed] [https://clinicaltrials.gov/study/NCT01029054 NCT01029054] |
+ | # '''ATLAS-MM:''' Dytfeld D, Wróbel T, Jamroziak K, Kubicki T, Robak P, Walter-Croneck A, Czyż J, Tyczyńska A, Druzd-Sitek A, Giannopoulos K, Nowicki A, Szczepaniak T, Łojko-Dankowska A, Matuszak M, Gil L, Puła B, Rybka J, Majcherek M, Usnarska-Zubkiewicz L, Szukalski Ł, Końska A, Zaucha JM, Walewski J, Mikulski D, Czabak O, Robak T, Lahoud OB, Zonder JA, Griffith K, Stefka A, Major A, Derman BA, Jakubowiak AJ. Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Feb;24(2):139-150. Epub 2023 Jan 12. [https://doi.org/10.1016/s1470-2045(22)00738-0 link to original article]'''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337122/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36642080/ PubMed] [https://clinicaltrials.gov/study/NCT02659293 NCT02659293] | ||
+ | ##'''HRQoL analysis:''' Kubicki T, Jamroziak K, Robak P, Czyż J, Tyczyńska A, Druzd-Sitek A, Giannopoulos K, Wróbel T, Nowicki A, Szczepaniak T, Łojko-Dankowska A, Matuszak M, Gil L, Puła B, Szukalski Ł, Końska A, Zaucha JM, Walewski J, Mikulski D, Czabak O, Robak T, Kruk-Kwapisz D, Derman BA, Major A, Jakubowiak AJ, Dytfeld D. Health-related quality of life in patients with multiple myeloma treated in the phase 3 ATLAS trial of post-transplant maintenance with carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone. Pol Arch Intern Med. 2024 May 28;134(5):16749. Epub 2024 May 14. [https://doi.org/10.20452/pamw.16749 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38747414/ PubMed] | ||
==Lenalidomide monotherapy {{#subobject:1bb17c|Regimen=1}}== | ==Lenalidomide monotherapy {{#subobject:1bb17c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, indefinite 10 mg 21/28 {{#subobject:7a71f8|Variant=1}}=== | ===Regimen variant #1, indefinite 10 mg 21/28 {{#subobject:7a71f8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2007.12.3463 Palumbo et al. 2007a] |
|2005 | |2005 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2009.22.7561 Palumbo et al. 2010] |
|2005-2007 | |2005-2007 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1112704 Palumbo et al. 2012 (MM-015)] |
− | |2007-2008 | + | |2007-02 to 2008-09 |
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_historical#Placebo|Placebo]] | |[[Multiple_myeloma_-_historical#Placebo|Placebo]] | ||
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1402888 Palumbo et al. 2014 (MPRvsMEL200)] |
|2007-2009 | |2007-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 41.9 vs 21.6 mo<br>(HR 0.47, 95% CI 0.33-0.65) |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566809/ Stewart et al. 2015 (ECOG E1A06)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566809/ Stewart et al. 2015 (ECOG E1A06)] | ||
|2008-2011 | |2008-2011 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(15)00389-7 Gay et al. 2015 (EMN-441)] |
|2009-2011 | |2009-2011 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#Lenalidomide_.26_Prednisone_.28RP.29_2|RP]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2015-08-662627 Magarotto et al. 2016 (EMN01)] |
|2009-2012 | |2009-2012 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |[[# | + | |[[#Lenalidomide_.26_Prednisone_.28RP.29_2|RP]] |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2015-11-679415 Zweegman et al. 2016 (HOVON87/NMSG18)] |
|2009-2012 | |2009-2012 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
|[[#Thalidomide_monotherapy|Thalidomide]] | |[[#Thalidomide_monotherapy|Thalidomide]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318225/ Jackson et al. 2018 (UK NCRI Myeloma XI)] | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318225/ Jackson et al. 2018 (UK NCRI Myeloma XI)] |
− | |2011-2017 | + | |rowspan=2|2011-01-13 to 2017-08-11 |
− | |style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | + | |1. [[Multiple_myeloma_-_null_regimens#Observation|Observation]] |
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (co-primary endpoint)<br>Median PFS: 39 vs 20 mo<br>(HR 0.46, 95% CI 0.41-0.53) |
+ | |- | ||
+ | |2. [[#Lenalidomide_.26_Vorinostat_999|Lenalidomide & Vorinostat]] | ||
+ | |style="background-color:#ffffbf"|Did not meet co-primary endpoint of PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1182/blood.2020009507 Larocca et al. 2021 (RV-MM-PI-0752)] | ||
+ | |2014-2017 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |[[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]; continuous | ||
+ | | style="background-color:#91cf60" |Seems to have superior EFS (primary endpoint)<br>Median EFS: 10.4 vs 6.9 mo<br>(HR 0.70, 95% CI 0.51-0.95) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Palumbo et al. 2007a & MM-015: [[Multiple_myeloma,_induction#MPR|MPR | + | *Palumbo et al. 2007a & MM-015: [[Multiple_myeloma,_induction#MPR|MPR]] induction x 9 |
− | *Palumbo et al. 2010: [[# | + | *Palumbo et al. 2010: [[#Lenalidomide_.26_Prednisone_.28RP.29|RP]] consolidation |
− | *MPRvsMEL200: [[#Tandem_melphalan.2C_then_auto_HSCT|Tandem high-dose melphalan with autologous hematopoietic stem cell transplants]] versus [[#MPR|MPR | + | *MPRvsMEL200: [[#Tandem_melphalan.2C_then_auto_HSCT|Tandem high-dose melphalan with autologous hematopoietic stem cell transplants]] versus [[#MPR|MPR]] consolidation |
− | *ECOG E1A06: [[Multiple_myeloma,_induction#MPR|mPR | + | *ECOG E1A06: [[Multiple_myeloma,_induction#MPR|mPR]] induction x 12 |
− | *EMN-441: [[#Tandem_melphalan.2C_then_auto_HSCT|Tandem high-dose melphalan with autologous hematopoietic cell transplants]] versus | + | *EMN-441: [[#Tandem_melphalan.2C_then_auto_HSCT|Tandem high-dose melphalan with autologous hematopoietic cell transplants]] versus [[#CRd_888|CRd consolidation]] |
− | *EMN01: [[Multiple_myeloma,_induction#CPR|CPR]] versus [[Multiple_myeloma,_induction#MPR|MPR]] versus [[Multiple_myeloma,_induction# | + | *EMN01: [[Multiple_myeloma,_induction#CPR|CPR]] versus [[Multiple_myeloma,_induction#MPR|MPR]] versus [[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] induction x 9 |
− | *HOVON87/NMSG18: [[Multiple_myeloma,_induction#MPR|MPR induction]] x 9 | + | *HOVON87/NMSG18: [[Multiple_myeloma,_induction#MPR|MPR]] induction x 9 |
+ | *RV-MM-PI-0752: [[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] induction x 9 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Varies depending on reference: | *Varies depending on reference: | ||
− | * | + | *MM-015: [[Aspirin]] 75 to 100 mg PO once per day |
− | * | + | *Palumbo et al. 2007a and Palumbo et al. 2010: [[Aspirin]] 100 mg PO once per day |
− | * | + | *ECOG E1A06: [[Aspirin]] was required (dose not specified) |
**''Full anticoagulation was used for patients at "higher risk" for DVT'' | **''Full anticoagulation was used for patients at "higher risk" for DVT'' | ||
− | * | + | *EMN01: [[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] at physician's discretion (mandatory) |
− | * | + | *ECOG E1A06: [[Pamidronate (Aredia)]] 90 mg IV once per month recommended for patients with "active bone disease" |
− | * | + | *Palumbo et al. 2007a: [[Ciprofloxacin (Cipro)]] 500 mg PO twice per day |
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Protocol variant #2, indefinite 15 mg per day {{#subobject:afeaa0|Variant=1}}=== | + | ===Protocol variant #2, indefinite 10 -> 15 mg per day with higher dose lead-in {{#subobject:afeaa0|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1114138 Attal et al. 2012 (IFM 2005-02)] |
|2006-2008 | |2006-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|[[Multiple_myeloma_-_historical#Placebo|Placebo]] | |[[Multiple_myeloma_-_historical#Placebo|Placebo]] | ||
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 41 vs 23 mo<br>(HR 0.50) |
|- | |- | ||
|} | |} | ||
''Note: this is "Maintenance Study 2" listed in the package insert.'' | ''Note: this is "Maintenance Study 2" listed in the package insert.'' | ||
− | ====Targeted therapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | + | ====Targeted therapy==== |
− | + | *[[Lenalidomide (Revlimid)]] as follows: | |
− | + | **Cycles 1 & 2: 25 mg PO once per day on days 1 to 21 | |
− | + | **Cycle 3: 10 mg PO once per day on days 1 to 90 | |
− | + | **Cycle 4 onwards: 15 mg PO once per day on days 1 to 90 | |
− | * | + | ====Supportive therapy==== |
− | |||
− | ====Supportive | ||
*"Thromboprophylaxis was not used" | *"Thromboprophylaxis was not used" | ||
− | + | '''28-day cycle for 2 cycles, then 90-day cycles''' | |
− | ''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen variant #3, indefinite | + | ===Regimen variant #3, indefinite 10 -> 15 mg per day {{#subobject:9d6a85|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,360: | Line 1,771: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744390/ McCarthy et al. 2012 (CALGB 100104)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744390/ McCarthy et al. 2012 (CALGB 100104)] | ||
|2005-2009 | |2005-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|[[Multiple_myeloma_-_historical#Placebo|Placebo]] | |[[Multiple_myeloma_-_historical#Placebo|Placebo]] | ||
− | |style="background-color:# | + | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 113.8 vs 84.1 mo<br>(HR 0.61, 95% CI 0.46-0.81)<br><br>Superior TTP (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | ''Note: this is "Maintenance Study 1" listed in the package insert.'' | + | ''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br> |
+ | ''Note: this is "Maintenance Study 1" listed in the package insert. There may be some dosing discrepancies between papers; this dose is the one described in the 2017 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|Melphalan with auto HSCT]] consolidation, within 100 to 120 days |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Lenalidomide (Revlimid)]] | + | *[[Lenalidomide (Revlimid)]] as follows: |
− | + | **Cycle 1: 10 mg PO once per day on days 1 to 90 | |
− | + | **Cycle 2 onwards: 15 mg PO once per day on days 1 to 90 | |
− | ====Supportive | + | ====Supportive therapy==== |
*Patients at high risk of deep venous thrombosis (DVT) or pulmonary embolism (PE) received [[Aspirin]], [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]], or [[Warfarin (Coumadin)]] unless contraindicated. High risk patients were defined as people with: history of diabetes, coronary artery disease, "DVT/PE, significant family history, performance status of at least 2, smoking history, use of oral contraceptives, and[/or] concurrent use of epoetin." | *Patients at high risk of deep venous thrombosis (DVT) or pulmonary embolism (PE) received [[Aspirin]], [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]], or [[Warfarin (Coumadin)]] unless contraindicated. High risk patients were defined as people with: history of diabetes, coronary artery disease, "DVT/PE, significant family history, performance status of at least 2, smoking history, use of oral contraceptives, and[/or] concurrent use of epoetin." | ||
− | + | '''90-day cycles''' | |
− | ''' | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 2 years of 25 mg 21/28 {{#subobject:537dbc|Variant=1}}=== | ===Regimen variant #4, 2 years of 25 mg 21/28 {{#subobject:537dbc|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6662597/ Korde et al. 2016 (NCI 12-C-0107)] |
− | |style="background-color:#91cf61"|Phase | + | |2011-2013 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6662597/ Korde et al. 2016 (NCI 11-C-0221)] |
− | |style="background-color:#91cf61"|Phase | + | |2011-2013 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#KRd|KRd]] x 8 | + | *Induction [[Multiple_myeloma,_induction#KRd|KRd]] x 8 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycle for up to 24 cycles''' | '''28-day cycle for up to 24 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #5, 1 year of 10 to 15 mg per day {{#subobject:99cf02|Variant=1}}=== | ===Regimen variant #5, 1 year of 10 to 15 mg per day {{#subobject:99cf02|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2013.54.8164 Roussel et al. 2014 (IFM 2008)] |
− | |style="background-color:#91cf61"|Phase | + | |2009 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ Attal et al. 2017 (IFM 2009)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2010-2012 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Thalidomide dose was increased only if the starting dose was tolerated.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#RVD|RVD | + | *[[#RVD|RVD]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day | + | *[[Lenalidomide (Revlimid)]] as follows: |
− | + | **Months 1 to 3: 10 mg PO once per day | |
+ | **Months 4 to 12: 15 mg PO once per day | ||
'''12-month course''' | '''12-month course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #6, indefinite 25 mg 21/28 {{#subobject:2650d7|Variant=1}}=== | ===Regimen variant #6, indefinite 25 mg 21/28 {{#subobject:2650d7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162553/ Jakubowiak et al. 2012 (UMCC 2009.056)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162553/ Jakubowiak et al. 2012 (UMCC 2009.056)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2009-2011 |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#KRd|KRd]] x 24 | + | *Induction [[Multiple_myeloma,_induction#KRd|KRd]] x 24 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foà R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. Epub 2007 Sep 4. [ | + | # Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foà R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. Epub 2007 Sep 4. [https://doi.org/10.1200/jco.2007.12.3463 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17785703/ PubMed] |
− | # Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [ | + | # Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [https://doi.org/10.1200/jco.2009.22.7561 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20048187/ PubMed] EudraCT 2005-004714-32 |
− | ## '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [ | + | ## '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [https://doi.org/10.1182/blood-2013-02-483073 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23775712/ PubMed] |
− | # '''CALGB 100104:''' McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. [https:// | + | # '''CALGB 100104:''' McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. [https://doi.org/10.1056/NEJMoa1114083 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1114083/suppl_file/nejmoa1114083_appendix.pdf link to supplementary appendix] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744390/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22571201/ PubMed] [https://clinicaltrials.gov/study/NCT00114101 NCT00114101] |
− | + | ## '''Update:''' Holstein SA, Jung SH, Richardson PG, Hofmeister CC, Hurd DD, Hassoun H, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, van Besien K, Gentile TG, Isola L, Maziarz RT, Bashey A, Landau H, Martin T, Qazilbash MH, Rodriguez C, McClune B, Schlossman RL, Smith SE, Hars V, Owzar K, Jiang C, Boyd M, Schultz C, Wilson M, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Linker C, Anderson KC, McCarthy PL. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial. Lancet Haematol. 2017 Sep;4(9):e431-e442. Epub 2017 Aug 17. [https://doi.org/10.1016/S2352-3026(17)30140-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5718627/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28826616/ PubMed] | |
− | + | # '''IFM2005-02:''' Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1782-91. [https://doi.org/10.1056/NEJMoa1114138 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22571202/ PubMed] [https://clinicaltrials.gov/study/NCT00430365 NCT00430365] | |
− | + | ## '''Update: Abstract:''' Michel Attal, MD, Valerie Cances Lauwers, Gerald Marit, Denis Caillot, Thierry Facon, MD, Cyrille Hulin, Philippe Moreau, MD, Claire Mathiot, Murielle Roussel, Catherine Payen, H. Avet-Loiseau and Jean Luc Harousseau. Maintenance Treatment with Lenalidomide After Transplantation for MYELOMA : Final Analysis of the IFM 2005-02. ASH 2010 Abstract 310. | |
− | # '''UMCC 2009.056:''' Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. Epub 2012 Jun 4. [ | + | # '''UMCC 2009.056:''' Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. Epub 2012 Jun 4. [https://doi.org/10.1182/blood-2012-04-422683 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162553/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22665938/ PubMed] [https://clinicaltrials.gov/study/NCT01029054 NCT01029054] |
− | # '''MM-015:''' Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. Erratum in: N Engl J Med. 2012 Jul 19;367(3):285. [https:// | + | # '''MM-015:''' Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. Erratum in: N Engl J Med. 2012 Jul 19;367(3):285. [https://doi.org/10.1056/NEJMoa1112704 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22571200/ PubMed] [https://clinicaltrials.gov/study/NCT00405756 NCT00405756] |
− | # '''IFM 2008:''' Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. [ | + | # '''IFM 2008:''' Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. [https://doi.org/10.1200/jco.2013.54.8164 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25024076/ PubMed] [https://clinicaltrials.gov/study/NCT01206205 NCT01206205] |
− | + | # '''MPRvsMEL200:''' Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. [https://doi.org/10.1056/NEJMoa1402888 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25184862/ PubMed] [https://clinicaltrials.gov/study/NCT00551928 NCT00551928] | |
− | # '''GMMG-MM5:''' Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, Munder M, Jauch A, Schurich B, Hielscher T, Merz M, Huegle-Doerr B, Seckinger A, Hose D, Hillengass J, Raab MS, Neben K, Lindemann HW, Zeis M, Gerecke C, Schmidt-Wolf IG, Weisel K, Scheid C, Salwender H, Goldschmidt H. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015 Aug;29(8):1721-9. Epub 2015 Mar 19. [https://doi.org/10.1038/leu.2015.80 link to original article] ''' | + | # '''GMMG-MM5:''' Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, Munder M, Jauch A, Schurich B, Hielscher T, Merz M, Huegle-Doerr B, Seckinger A, Hose D, Hillengass J, Raab MS, Neben K, Lindemann HW, Zeis M, Gerecke C, Schmidt-Wolf IG, Weisel K, Scheid C, Salwender H, Goldschmidt H. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015 Aug;29(8):1721-9. Epub 2015 Mar 19. [https://doi.org/10.1038/leu.2015.80 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25787915/ PubMed] EudraCT 2010-019173-16 |
− | ## ''' | + | ## '''Subgroup analysis:''' Merz M, Salwender H, Haenel M, Mai EK, Bertsch U, Kunz C, Hielscher T, Blau IW, Scheid C, Hose D, Seckinger A, Jauch A, Hillengass J, Raab MS, Schurich B, Munder M, Schmidt-Wolf IG, Gerecke C, Lindemann HW, Zeis M, Weisel K, Duerig J, Goldschmidt H. Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial. Haematologica. 2015 Jul;100(7):964-9. Epub 2015 Apr 3. [https://doi.org/10.3324/haematol.2015.124347 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486231/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25840597/ PubMed] |
− | # ''' | + | ## '''Update:''' Goldschmidt H, Mai EK, Dürig J, Scheid C, Weisel KC, Kunz C, Bertsch U, Hielscher T, Merz M, Munder M, Lindemann HW, Hügle-Dörr B, Tichy D, Giesen N, Hose D, Seckinger A, Huhn S, Luntz S, Jauch A, Elmaagacli A, Rabold B, Fuhrmann S, Brossart P, Goerner M, Bernhard H, Hoffmann M, Hillengass J, Raab MS, Blau IW, Hänel M, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG). Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. Leukemia. 2020 Jul;34(7):1853-1865. Epub 2020 Feb 7. [https://doi.org/10.1038/s41375-020-0724-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32034285/ PubMed] |
− | + | # '''ECOG E1A06:''' Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, Rajkumar SV. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015 Sep 10;126(11):1294-301. Epub 2015 Jul 8. [https://doi.org/10.1182/blood-2014-12-613927 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26157076/ PubMed] [https://clinicaltrials.gov/study/NCT00602641 NCT00602641] | |
− | # ''' | + | # '''EMN-441:''' Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. [https://doi.org/10.1016/S1470-2045(15)00389-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26596670/ PubMed] [https://clinicaltrials.gov/study/NCT01091831 NCT01091831] |
− | + | # '''EMN01:''' Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. Epub 2016 Jan 4. [https://doi.org/10.1182/blood-2015-08-662627 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26729895/ PubMed] [https://clinicaltrials.gov/study/NCT01093196 NCT01093196] | |
− | # ''' | + | # '''HOVON87/NMSG18:''' Zweegman S, van der Holt B, Mellqvist UH, Salomo M, Bos GM, Levin MD, Visser-Wisselaar H, Hansson M, van der Velden AW, Deenik W, Gruber A, Coenen JL, Plesner T, Klein SK, Tanis BC, Szatkowski DL, Brouwer RE, Westerman M, Leys MR, Sinnige HA, Haukås E, van der Hem KG, Durian MF, Mattijssen EV, van de Donk NW, Stevens-Kroef MJ, Sonneveld P, Waage A. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 Mar 3;127(9):1109-16. Epub 2016 Jan 22. [https://doi.org/10.1182/blood-2015-11-679415 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26802176/ PubMed] EudraCT 2007-004007-34 |
+ | # '''Abstract: Meta-analysis:''' Michel Attal, Antonio Palumbo, Sarah A. Holstein, Valerie Lauwers-Cances, Maria Teresa Petrucci, Paul G. Richardson, Cyrille Hulin, Patrizia Tosi, Kenneth Carl Anderson, Denis Caillot, Valeria Magarotto, Philippe Moreau, Gerald Marit, Zhinuan Yu, Philip L. McCarthy. Lenalidomide (LEN) maintenance (MNTC) after high-dose melphalan and autologous stem cell transplant (ASCT) in multiple myeloma (MM): A meta-analysis (MA) of overall survival (OS). J Clin Oncol 34, 2016 (suppl; abstr 8001) [https://doi.org/10.1200/JCO.2016.34.15_suppl.8001 link to abstract] | ||
<!-- | <!-- | ||
− | # '''Abstract:''' Korde, Neha; Zingone, Adriana; Kwok, Mary; Manasanch, Elisabet E.; Costello, Rene; Zuchlinski, Diamond; Mulquin, Marcia; Maric, Irina; Calvo, Katherine R; Braylan, Raul C.; Yuan, Constance; Tembhare, Prashant Ramesh; Stetler-Stevenson, Maryalice; Arthur, Diane C; Raffeld, Mark; Xi, Liqiang; Choyke, Peter; Kurdziel, Karen; Lindenberg, Liza; Steinberg, Seth M.; Roschewski, Mark; Landgren, Ola. Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone (CRd) in Newly Diagnosed Multiple Myeloma (MM) Patients ASH Annual Meeting Abstracts 2012 120: 732 [ | + | # '''Abstract:''' Korde, Neha; Zingone, Adriana; Kwok, Mary; Manasanch, Elisabet E.; Costello, Rene; Zuchlinski, Diamond; Mulquin, Marcia; Maric, Irina; Calvo, Katherine R; Braylan, Raul C.; Yuan, Constance; Tembhare, Prashant Ramesh; Stetler-Stevenson, Maryalice; Arthur, Diane C; Raffeld, Mark; Xi, Liqiang; Choyke, Peter; Kurdziel, Karen; Lindenberg, Liza; Steinberg, Seth M.; Roschewski, Mark; Landgren, Ola. Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone (CRd) in Newly Diagnosed Multiple Myeloma (MM) Patients ASH Annual Meeting Abstracts 2012 120: 732 [https://doi.org/10.1182/blood.V120.21.732.732 link to abstract] --> |
− | # '''NCI 11-C-0221; NCI 12-C-0107:''' Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With carfilzomib-lenalidomide-dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. [ | + | # '''NCI 11-C-0221:''' Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With carfilzomib-lenalidomide-dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. [https://doi.org/10.1001/jamaoncol.2015.2010 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6662597/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26181891/ PubMed] [https://clinicaltrials.gov/study/NCT01402284 NCT01402284] |
− | # '''IFM 2009:''' Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. [https:// | + | # '''NCI 12-C-0107:''' Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With carfilzomib-lenalidomide-dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. [https://doi.org/10.1001/jamaoncol.2015.2010 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6662597/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26181891/ PubMed] [https://clinicaltrials.gov/study/NCT01572480 NCT01572480] |
− | # '''UK NCRI Myeloma XI:''' Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Hockaday A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ; UK NCRI Haemato-oncology Clinical Studies Group. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019 Jan;20(1):57-73. Epub 2018 Dec 14. [https://www. | + | # '''IFM 2009:''' Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. [https://doi.org/10.1056/NEJMoa1611750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6201242/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28379796/ PubMed] [https://clinicaltrials.gov/study/NCT01191060 NCT01191060] |
+ | # '''UK NCRI Myeloma XI:''' Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Hockaday A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ; UK NCRI Haemato-oncology Clinical Studies Group. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019 Jan;20(1):57-73. Epub 2018 Dec 14. [https://doi.org/10.1016/S1470-2045(18)30687-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30559051/ PubMed] [https://clinicaltrials.gov/study/NCT01554852 NCT01554852] | ||
+ | ##'''Update:''' Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Waterhouse A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Allotey D, Shafeek S, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Clinical Studies Group UNHO. Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial. Haematologica. 2021 Jul 1;106(7):1957-1967. [https://doi.org/10.3324/haematol.2020.247130 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8252959/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32499244/ PubMed] | ||
+ | ##'''Update:''' Jenner MW, Pawlyn C, Davies FE, Menzies T, Hockaday A, Olivier C, Jones JR, Karunanithi K, Lindsay J, Kishore B, Cook G, Drayson MT, Kaiser MF, Owen RG, Gregory W, Cairns DA, Morgan GJ, Jackson GH; UK National Cancer Research Institute (NCRI) Haemato-oncology Clinical Studies Group. The addition of vorinostat to lenalidomide maintenance for patients with newly diagnosed multiple myeloma of all ages: results from 'Myeloma XI', a multicentre, open-label, randomised, phase III trial. Br J Haematol. 2023 Apr;201(2):267-279. Epub 2022 Dec 21. [https://doi.org/10.1111/bjh.18600 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10952726/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36541152/ PubMed] | ||
+ | #'''RV-MM-PI-0752:''' Larocca A, Bonello F, Gaidano G, D'Agostino M, Offidani M, Cascavilla N, Capra A, Benevolo G, Tosi P, Galli M, Marasca R, Giuliani N, Bernardini A, Antonioli E, Rota-Scalabrini D, Cellini C, Pompa A, Monaco F, Patriarca F, Caravita di Toritto T, Corradini P, Tacchetti P, Boccadoro M, Bringhen S. Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Blood. 2021 Jun 3;137(22):3027-3036. [https://doi.org/10.1182/blood.2020009507 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33739404/ PubMed] [https://clinicaltrials.gov/study/NCT02215980 NCT02215980] | ||
+ | # '''AURIGA:''' [https://clinicaltrials.gov/study/NCT03901963 NCT03901963] | ||
+ | # '''DRAMMATIC:''' [https://clinicaltrials.gov/study/NCT04071457 NCT04071457] | ||
+ | # '''LenaMain-Trial:''' [https://clinicaltrials.gov/study/NCT00891384 NCT00891384] | ||
+ | # '''MagnetisMM-7:''' [https://clinicaltrials.gov/study/NCT05317416 NCT05317416] | ||
+ | # '''MajesTEC-4:''' [https://clinicaltrials.gov/study/NCT05243797 NCT05243797] | ||
− | ==Rd {{#subobject:945256|Regimen=1}}== | + | ==Lenalidomide & Dexamethasone (Rd) {{#subobject:945256|Regimen=1}}== |
− | {| class="wikitable" style=" | + | Rd: '''<u>R</u>'''evlimid (Lenalidomide) & low-dose '''<u>d</u>'''examethasone |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:2yeloc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s2352-3026(23)00366-6 Mai et al. 2024 (GMMG-HD6)] | ||
+ | |2015-06-29 to 2017-09-11 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Elo-Rd_999|Elo-Rd]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[#RVD|RVd]] consolidation x 2 versus [[#Elo-RVd_999|Elo-RVd]] consolidation x 2 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lenalidomide (Revlimid)]] as follows: | ||
+ | **Cycles 1 to 3: 10 mg PO once per day on days 1 to 28 | ||
+ | **Cycles 4 to 26: 15 mg PO once per day on days 1 to 28 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] as follows: | ||
+ | **Cycles 1 to 6: 12 mg PO once per day on days 1 & 15 | ||
+ | **Cycles 7 to 26: 12 mg PO once on day 1 | ||
+ | '''28-day cycle for 26 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 15/20 {{#subobject:2yceb4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1182/blood.2022019531 Rosiñol et al. 2023 (GEM2014MAIN)] | ||
+ | |2014-11 to 2017-05 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#IRd|IRd]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS12 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen {{#subobject:ef4eb4|Variant=1}}=== | + | ====Preceding treatment==== |
− | {| class="wikitable" style="width: | + | *[[#RVD|VRd]] consolidation x 2 |
− | !style="width: | + | </div> |
− | !style="width: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
+ | *[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 9 to 12 | ||
+ | '''28-day cycle for 24 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Subsequent treatment==== | ||
+ | *GEM2014MAIN, negative MRD at 2 years: [[Multiple_myeloma_-_null_regimens#Observation|No further treatment]] | ||
+ | *GEM2014MAIN, positive MRD at 2 years: [[#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] continuation x 36 cycles (60 cycles total) | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 25/40 indefinite {{#subobject:ef4eb4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5546834/ Durie et al. 2016 (SWOG S0777)] |
− | | style="background-color:#91cf61" |Non-randomized | + | |2008-2012 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction# | + | *Induction [[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] x 6 versus [[Multiple_myeloma,_induction#RVD|VRd]] x 8 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, indefinite with renal adjustment {{#subobject:e3c3b4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2400712 Facon et al. 2024 (IMROZ)] | ||
+ | |2017-12 to 2019-03 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Induction [[Multiple_myeloma,_induction#RVD|RVd]] x 4 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lenalidomide (Revlimid)]] by the following laboratory-based criteria: | ||
+ | **eGFR 60 mL/min/1.73m<sup>2</sup> or more: 25 mg PO once per day on days 1 to 21 | ||
+ | **eGFR 30 up to 60 mL/min/1.73m<sup>2</sup>: 10 mg PO once per day on days 1 to 21 | ||
+ | ====Glucocorticoid therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''SWOG S0777:''' Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017 Feb 4;389(10068):519-527. Epub 2016 Dec 22. [https://www. | + | # '''SWOG S0777:''' Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017 Feb 4;389(10068):519-527. Epub 2016 Dec 22. [https://doi.org/10.1016/S0140-6736(16)31594-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5546834/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28017406/ PubMed] [https://clinicaltrials.gov/study/NCT00644228 NCT00644228] |
+ | # '''GEM2014MAIN:''' Rosiñol L, Oriol A, Ríos R, Blanchard MJ, Jarque I, Bargay J, Hernández MT, Cabañas V, Carrillo-Cruz E, Sureda A, Martínez-López J, Krsnik I, González ME, Casado LF, Martí JM, Encinas C, de Arriba F, Palomera L, Sampol A, González-Montes Y, Cabezudo E, Paiva B, Puig N, Cedena MT, de la Cruz J, Mateos MV, San Miguel J, Lahuerta JJ, Bladé J. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood. 2023 Nov 2;142(18):1518-1528. Epub 2023 Jul 28. [https://doi.org/10.1182/blood.2022019531 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37506339/ PubMed] [https://clinicaltrials.gov/study/NCT02406144 NCT02406144] | ||
+ | # '''GMMG-HD6:''' Mai EK, Goldschmid H, Miah K, Bertsch U, Besemer B, Hänel M, Krzykalla J, Fenk R, Schlenzka J, Munder M, Dürig J, Blau IW, Huhn S, Hose D, Jauch A, Kunz C, Mann C, Weinhold N, Scheid C, Schroers R, von Metzler I, Schieferdecker A, Thomalla J, Reimer P, Mahlberg R, Graeven U, Kremers S, Martens UM, Kunz C, Hensel M, Benner A, Seidel-Glätzer A, Weisel KC, Raab MS, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG) HD6 investigators. Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e101-e113. Erratum in: Lancet Haematol. 2024 Mar;11(3):e181. [https://doi.org/10.1016/s2352-3026(23)00366-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38302221/ PubMed] [https://clinicaltrials.gov/study/NCT02495922 NCT02495922] | ||
+ | #'''IMROZ:''' Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hájek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Brégeault MF, Macé S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Jun 3. Epub ahead of print. [https://doi.org/10.1056/nejmoa2400712 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38832972/ PubMed] [https://clinicaltrials.gov/study/NCT03319667 NCT03319667] | ||
− | ==RP {{#subobject:6261f9|Regimen=1}}== | + | ==Lenalidomide & Prednisone (RP) {{#subobject:6261f9|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
RP: '''<u>R</u>'''evlimid (Lenalidomide) & '''<u>P</u>'''rednisone | RP: '''<u>R</u>'''evlimid (Lenalidomide) & '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, prednisone 25 mg every other day {{#subobject:2cd1c5|Variant=1}}=== | ===Regimen variant #1, prednisone 25 mg every other day {{#subobject:2cd1c5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2015-08-662627 Magarotto et al. 2016 (EMN01)] |
|2009-2012 | |2009-2012 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Lenalidomide_monotherapy|Lenalidomide]] | |[[#Lenalidomide_monotherapy|Lenalidomide]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#CPR|CPR]] x 9 versus [[Multiple_myeloma,_induction#MPR|MPR]] x 9 versus [[Multiple_myeloma,_induction# | + | *Induction [[Multiple_myeloma,_induction#CPR|CPR]] x 9 versus [[Multiple_myeloma,_induction#MPR|MPR]] x 9 versus [[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]] x 9 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | *[[Prednisone (Sterapred)]] 25 mg PO once every other day | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] 25 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 | |
− | ====Supportive | + | ====Supportive therapy==== |
*[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] at physician's discretion (mandatory) | *[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] at physician's discretion (mandatory) | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, prednisone 25 mg TIW {{#subobject:5276c5|Variant=1}}=== | ===Regimen variant #2, prednisone 25 mg TIW {{#subobject:5276c5|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1038/leu.2012.271 Falco et al. 2012] | |[https://doi.org/10.1038/leu.2012.271 Falco et al. 2012] | ||
|2008-2009 | |2008-2009 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#MPR|MPR | + | *[[#MPR|MPR]] consolidation x 6 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | *[[Prednisone (Sterapred)]] 25 mg PO three times per week | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] 25 mg PO three times per week on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 | |
− | ====Supportive | + | ====Supportive therapy==== |
− | *Thromboprophylaxis: [[Aspirin]] 100 mg PO once per day, taken during | + | *Thromboprophylaxis: [[Aspirin]] 100 mg PO once per day, taken during lenalidomide treatment (unclear from protocol if this also means off weeks) |
*Antiviral prophylaxis if history of VZV. | *Antiviral prophylaxis if history of VZV. | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, prednisone 50 mg every other day {{#subobject:2acd15|Variant=1}}=== | ===Regimen variant #3, prednisone 50 mg every other day {{#subobject:2acd15|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(15)00389-7 Gay et al. 2015 (EMN-441)] |
|2009-2011 | |2009-2011 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[#Lenalidomide_monotherapy|Lenalidomide]] | |[[#Lenalidomide_monotherapy|Lenalidomide]] | ||
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS<br>Median PFS: 37.5 vs 28.5 mo<br>(HR 0.84, 95% CI 0.59-1.20) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem high-dose melphalan with autologous hematopoietic stem cell transplants]] versus | + | *[[#Tandem_melphalan.2C_then_auto_HSCT|Tandem high-dose melphalan with autologous hematopoietic stem cell transplants]] versus [[#CRd_888|CRd]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21 | ||
− | *[[Prednisone (Sterapred)]] 50 mg PO once every other day | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 | |
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Falco P, Cavallo F, Larocca A, Rossi D, Guglielmelli T, Rocci A, Grasso M, Siez ML, De Paoli L, Oliva S, Molica S, Mina R, Gay F, Benevolo G, Musto P, Omedè P, Freilone R, Bringhen S, Carella AM, Gaidano G, Boccadoro M, Palumbo A. Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. 2013 Mar;27(3):695-701. Epub 2012 Sep 21. [https://doi.org/10.1038/leu.2012.271 link to original article] ''' | + | # Falco P, Cavallo F, Larocca A, Rossi D, Guglielmelli T, Rocci A, Grasso M, Siez ML, De Paoli L, Oliva S, Molica S, Mina R, Gay F, Benevolo G, Musto P, Omedè P, Freilone R, Bringhen S, Carella AM, Gaidano G, Boccadoro M, Palumbo A. Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. 2013 Mar;27(3):695-701. Epub 2012 Sep 21. [https://doi.org/10.1038/leu.2012.271 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22996335/ PubMed] |
− | # '''EMN-441:''' Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. [https:// | + | # '''EMN-441:''' Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. [https://doi.org/10.1016/S1470-2045(15)00389-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26596670/ PubMed] [https://clinicaltrials.gov/study/NCT01091831 NCT01091831] |
− | # '''EMN01:''' Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. Epub 2016 Jan 4. [ | + | # '''EMN01:''' Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. Epub 2016 Jan 4. [https://doi.org/10.1182/blood-2015-08-662627 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26729895/ PubMed] [https://clinicaltrials.gov/study/NCT01093196 NCT01093196] |
− | |||
==RVD {{#subobject:416bec|Regimen=1}}== | ==RVD {{#subobject:416bec|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone | RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone | ||
<br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide) | <br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide) | ||
<br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone | <br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone | ||
<br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | <br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 3-year course {{#subobject:8392a1|Variant=1}}=== | ===Regimen variant #1, 3-year course {{#subobject:8392a1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879104/ Nair et al. 2010 (2006-66)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879104/ Nair et al. 2010 (2006-66)] | ||
+ | |2006-11 to 2008-09 | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *VTD-PACE consolidation (per Total Therapy 3 protocol) | + | *[[#VTD-PACE|VTD-PACE]] consolidation (per Total Therapy 3 protocol) |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 20, then 5 mg PO once per day on days 21 to 28 | *[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 20, then 5 mg PO once per day on days 21 to 28 | ||
*[[Bortezomib (Velcade)]] as follows: | *[[Bortezomib (Velcade)]] as follows: | ||
− | ** | + | **Cycles 1 to 13: 1 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 |
− | ** | + | **Cycles 14 to 39: 1 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 |
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] as follows: | *[[Dexamethasone (Decadron)]] as follows: | ||
− | + | **Cycles 1 to 13: 20 mg (route not specified) once per day on days 1 to 4, 8 to 11 | |
− | '''3 | + | **Cycles 14 to 39: 20 mg (route not specified) once per day on days 1, 8, 15, 22 |
− | + | ||
+ | '''28-day cycle for 39 cycles (3 years)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, Indefinite {{#subobject:b97d68|Variant=1}}=== | ===Regimen variant #2, Indefinite {{#subobject:b97d68|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324254/ Richardson et al. 2010] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324254/ Richardson et al. 2010 (DFCI 06-150)] |
− | |style="background-color:#91cf61"|Phase | + | |2006-2008 |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#RVD|RVD]] x 4 to 8 | + | *Induction [[Multiple_myeloma,_induction#RVD|RVD]] x 4 to 8 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg (or previously tolerated dose) PO once per day on days 1 to 14 | *[[Lenalidomide (Revlimid)]] 25 mg (or previously tolerated dose) PO once per day on days 1 to 14 | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> (or previously tolerated dose) IV once per day on days 1 & 8 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> (or previously tolerated dose) IV once per day on days 1 & 8 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 20 mg (or previously tolerated dose) PO once per day on days 1, 2, 8, 9 | *[[Dexamethasone (Decadron)]] 20 mg (or previously tolerated dose) PO once per day on days 1, 2, 8, 9 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Aspirin]] 81 mg or 325 mg PO once per day on days 1 to 21 |
− | *[[Aspirin]] 81 mg or 325 mg PO once per day | + | *[[:Category:Antivirals |Antiviral therapy]], such as [[Acyclovir (Zovirax)]] 400 mg PO once per day on days 1 to 21 |
− | *[[:Category:Antivirals |Antiviral therapy]], such as [[Acyclovir (Zovirax)]] 400 mg PO once per day | ||
*[[:Category:Bisphosphonates|Bisphosphonate]] | *[[:Category:Bisphosphonates|Bisphosphonate]] | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''2006-66:''' Nair B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Szymonifka J, Hoering A, Alsayed Y, Waheed S, Crowley J, Barlogie B. Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance. Blood. 2010 May 27;115(21):4168-73. Epub 2010 Feb 2. [ | + | # '''2006-66:''' Nair B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Szymonifka J, Hoering A, Alsayed Y, Waheed S, Crowley J, Barlogie B. Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance. Blood. 2010 May 27;115(21):4168-73. Epub 2010 Feb 2. [https://doi.org/10.1182/blood-2009-11-255620 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879104/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20124509/ PubMed] |
− | # Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. Epub 2010 Apr 12. [ | + | # '''DFCI 06-150:''' Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. Epub 2010 Apr 12. [https://doi.org/10.1182/blood-2010-02-268862 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324254/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20385792/ PubMed] [https://clinicaltrials.gov/study/NCT00378105 NCT00378105] |
− | # '''Retrospective:''' Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. [https://doi.org/10.1038/leu.2013.335 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24220275 PubMed] | + | # '''Retrospective:''' Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. [https://doi.org/10.1038/leu.2013.335 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24220275/ PubMed] |
==Thalidomide monotherapy {{#subobject:9f2412|Regimen=1}}== | ==Thalidomide monotherapy {{#subobject:9f2412|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 50 mg/day x 2 years {{#subobject:c09c56|Variant=1}}=== | ===Regimen variant #1, 50 mg/day x 2 years {{#subobject:c09c56|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (HOVON-65)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Bortezomib_monotherapy_2|Bortezomib]] | |[[#Bortezomib_monotherapy_2|Bortezomib]] | ||
− | |style="background-color:#d73027"|Inferior PFS | + | |style="background-color:#d73027"|Inferior PFS<sup>1</sup> |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (GMMG-HD4)] |
|2005-2008 | |2005-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Bortezomib_monotherapy_2|Bortezomib]] | |[[#Bortezomib_monotherapy_2|Bortezomib]] | ||
− | |style="background-color:#d73027"|Inferior PFS | + | |style="background-color:#d73027"|Inferior PFS<sup>1</sup> |
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>In the initial publication, this arm seemed to have an overall survival disadvantage; this was no longer present in the updated report of 2017; PFS was the primary endpoint.''<br> |
+ | ''Note: Observed efficacy is for induction PAD, then transplant, then maintenance bortezomib compared with induction VAD, then transplant, then maintenance thalidomide. Treatment starts 4 weeks after the final autologous hematopoietic stem cell transplant. HOVON-65/GMMG-HD4 was a single phase 3 RCT but the consolidation was different by group, so is reported here as 2 distinct trials.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *HOVON-65: [[# | + | *HOVON-65: [[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with autologous hematopoietic stem cell transplant]] consolidation |
− | *GMMG-HD4: [[#Tandem_melphalan.2C_then_auto_HSCT|High-dose melphalan with tandem autologous hematopoietic stem cell transplants]] | + | *GMMG-HD4: [[#Tandem_melphalan.2C_then_auto_HSCT|High-dose melphalan with tandem autologous hematopoietic stem cell transplants]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day | ||
− | |||
'''2-year course''' | '''2-year course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 50 mg/d, indefinite {{#subobject:dbd3f3|Variant=1}}=== | ===Regimen variant #2, 50 mg/d, indefinite {{#subobject:dbd3f3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2009-05-222539 Lokhorst et al. 2009 (HOVON-50)] |
|2001-2005 | |2001-2005 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Complex_multipart_regimens#HOVON-50|See link]] | |[[Complex_multipart_regimens#HOVON-50|See link]] | ||
|style="background-color:#1a9850"|[[Complex_multipart_regimens#HOVON-50|See link]] | |style="background-color:#1a9850"|[[Complex_multipart_regimens#HOVON-50|See link]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2009.26.1610 Wijermans et al. 2010 (HOVON 49)] |
|2002-2007 | |2002-2007 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *HOVON 49: [[Multiple_myeloma,_induction#MPT|MPT]] x 8 | + | *HOVON 49: Induction [[Multiple_myeloma,_induction#MPT|MPT]] x 8 |
− | *HOVON-50: [[Multiple_myeloma,_consolidation_and_maintenance# | + | *HOVON-50: [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan_monotherapy.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*'''HOVON 49:''' [[:Category:Bisphosphonates|Bisphosphonate]] use recommended with [[Pamidronate (Aredia)]] or [[Clodronate (Bonefos)]]; "a maximum treatment period of 2 years was recommended in patients without active disease." | *'''HOVON 49:''' [[:Category:Bisphosphonates|Bisphosphonate]] use recommended with [[Pamidronate (Aredia)]] or [[Clodronate (Bonefos)]]; "a maximum treatment period of 2 years was recommended in patients without active disease." | ||
*'''HOVON 49:''' During maintenance therapy, "low-dose [[Aspirin]] was advised" | *'''HOVON 49:''' During maintenance therapy, "low-dose [[Aspirin]] was advised" | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 50 -> 100 mg/d, indefinite {{#subobject:24fe5b|Variant=1}}=== | ===Regimen variant #3, 50 -> 100 mg/d, indefinite {{#subobject:24fe5b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,698: | Line 2,256: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639680/ Morgan et al. 2010 (MRC Myeloma IX)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639680/ Morgan et al. 2010 (MRC Myeloma IX)] | ||
|2003-2007 | |2003-2007 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS<sup>1</sup> (co-primary endpoint)<br>Median PFS: 23 vs 15 mo<br>(HR 0.69, 95% CI 0.58-0.82) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the update e-published on 2011 Oct 20.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | * | + | *MRC Myeloma IX, intensive treatment pathway: [[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic stem cell transplant]] consolidation |
− | * | + | *MRC Myeloma IX, non-intensive treatment pathway: Induction [[Multiple_myeloma,_induction#CTD|CTDa]] versus [[Multiple_myeloma_-_historical#MP_.28Prednisolone.29|MP]] |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] as follows: | *[[Thalidomide (Thalomid)]] as follows: | ||
− | ** | + | **Cycle 1: 50 mg PO once per day on days 1 to 28 |
− | ** | + | **Cycle 2 onwards: 100 mg PO once per day on days 1 to 28 |
− | + | '''28-day cycles''' | |
− | ''' | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 100 mg/day x 3 years {{#subobject:5b0623|Variant=1}}=== | ===Regimen variant #4, 100 mg/day x 3 years {{#subobject:5b0623|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | |rowspan=2|[https://doi.org/10.1182/blood-2012-02-408922 Rosiñol et al. 2012 (GEM05/MENOS65)] |
|rowspan=2|2006-2009 | |rowspan=2|2006-2009 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ooc) |
|1. [[Multiple_myeloma_-_historical#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]] | |1. [[Multiple_myeloma_-_historical#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|2. [[#VT|TV]] | |2. [[#VT|TV]] | ||
− | |style="background-color:#fc8d59"|Seems to have inferior PFS ( | + | |style="background-color:#fc8d59"|Seems to have inferior PFS<sup>1</sup> (secondary endpoint) |
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for GEM05/MENOS65 is based on the 2017 update.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous HSCT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 100 mg PO once per day | *[[Thalidomide (Thalomid)]] 100 mg PO once per day | ||
− | |||
'''3-year course''' | '''3-year course''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #5, 100 mg/d, indefinite {{#subobject:596043|Variant=1}}=== | ===Regimen variant #5, 100 mg/d, indefinite {{#subobject:596043|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(06)68338-4 Palumbo et al. 2006 (GISMM2001-A)] |
|2002-2005 | |2002-2005 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
Line 1,756: | Line 2,321: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566809/ Stewart et al. 2015 (ECOG E1A06)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566809/ Stewart et al. 2015 (ECOG E1A06)] | ||
|2008-2011 | |2008-2011 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2015-11-679415 Zweegman et al. 2016 (HOVON87/NMSG18)] |
|2009-2012 | |2009-2012 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Lenalidomide_monotherapy|Lenalidomide]] | |[[#Lenalidomide_monotherapy|Lenalidomide]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *GISMM2001-A: [[Multiple_myeloma,_induction#MPT|MPT]] x 6 | + | *GISMM2001-A: Induction [[Multiple_myeloma,_induction#MPT|MPT]] x 6 |
− | *ECOG E1A06: [[Multiple_myeloma,_induction#MPT|MPT]] x 12 | + | *ECOG E1A06: Induction [[Multiple_myeloma,_induction#MPT|MPT]] x 12 |
− | *HOVON87/NMSG18: [[Multiple_myeloma,_induction#MPT|MPT]] x 9 | + | *HOVON87/NMSG18: Induction [[Multiple_myeloma,_induction#MPT|MPT]] x 9 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 100 mg PO once per day | *[[Thalidomide (Thalomid)]] 100 mg PO once per day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Per ECOG E1A06, [[Aspirin]] was required (dose not specified) | *Per ECOG E1A06, [[Aspirin]] was required (dose not specified) | ||
**Per ECOG E1A06, full anticoagulation was used for patients at "higher risk" for DVT | **Per ECOG E1A06, full anticoagulation was used for patients at "higher risk" for DVT | ||
*Per ECOG E1A06, [[Pamidronate (Aredia)]] 90 mg IV once per month recommended for patients with "active bone disease" | *Per ECOG E1A06, [[Pamidronate (Aredia)]] 90 mg IV once per month recommended for patients with "active bone disease" | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #6, 400 mg/day x 18 months {{#subobject:962746|Variant=1}}=== | ===Regimen variant #6, 400 mg/day x 18 months {{#subobject:962746|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1038/sj.bmt.1705339 Sahebi et al. 2006] | |[https://doi.org/10.1038/sj.bmt.1705339 Sahebi et al. 2006] | ||
− | |style="background-color:#91cf61"|Phase | + | |2001-05 to 2004-01 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic stem cell transplant]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day, escalated by 50 mg every week to a target dose of 400 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day, escalated by 50 mg every week to a target dose of 400 mg PO once per day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[:Category:Bisphosphonates|Bisphosphonate]] once per month | *[[:Category:Bisphosphonates|Bisphosphonate]] once per month | ||
*Vitamin B6 | *Vitamin B6 | ||
− | |||
'''18 months of treatment or 6 months past CR, whichever comes first''' | '''18 months of treatment or 6 months past CR, whichever comes first''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #7, 400 mg/d, indefinite {{#subobject:767bfd|Variant=1}}=== | ===Regimen variant #7, 400 mg/d, indefinite {{#subobject:767bfd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2006-05-022962 Attal et al. 2006 (IFM 99-02)] |
|2000-2003 | |2000-2003 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | + | |1. [[Multiple_myeloma_-_null_regimens#Observation|Observation]]<br>2. [[#Pamidronate_monotherapy_888|Pamidronate]] |
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *VAD x 3 to 4, then [[#Tandem_melphalan.2C_then_auto_HSCT|high-dose melphalan with tandem autologous hematopoietic stem cell transplant]] | + | *Induction [[Multiple_myeloma_-_historical#VAD|VAD]] x 3 to 4, then [[#Tandem_melphalan.2C_then_auto_HSCT|high-dose melphalan with tandem autologous hematopoietic stem cell transplant]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Thalidomide (Thalomid)]] 400 mg PO once per day | + | *[[Thalidomide (Thalomid)]] 400 mg PO once per day on days 1 to 28 |
− | ** | + | ====Supportive therapy==== |
− | + | *[[Pamidronate (Aredia)]] 90 mg IV once on day 1 | |
− | + | '''28-day cycles''' | |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Thalidomide dose reductions to a minimum of 50 mg PO once per day were allowed | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''GISMM2001-A:''' Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825-31. [https:// | + | # '''GISMM2001-A:''' Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825-31. [https://doi.org/10.1016/S0140-6736(06)68338-4 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16530576/ PubMed] [https://clinicaltrials.gov/study/NCT00232934 NCT00232934] |
− | ## '''Update:''' Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14. Epub 2008 May 27. [ | + | ## '''Update:''' Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14. Epub 2008 May 27. [https://doi.org/10.1182/blood-2008-04-149427 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18505783/ PubMed] |
− | # Sahebi F, Spielberger R, Kogut NM, Fung H, Falk PM, Parker P, Krishnan A, Rodriguez R, Nakamura R, Nademanee A, Popplewell L, Frankel P, Ruel C, Tin R, Ilieva P, Forman SJ, Somlo G. Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant in patients with multiple myeloma. Bone Marrow Transplant. 2006 May;37(9):825-9. [https://doi.org/10.1038/sj.bmt.1705339 link to original article] ''' | + | # Sahebi F, Spielberger R, Kogut NM, Fung H, Falk PM, Parker P, Krishnan A, Rodriguez R, Nakamura R, Nademanee A, Popplewell L, Frankel P, Ruel C, Tin R, Ilieva P, Forman SJ, Somlo G. Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant in patients with multiple myeloma. Bone Marrow Transplant. 2006 May;37(9):825-9. [https://doi.org/10.1038/sj.bmt.1705339 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16565743/ PubMed] |
− | # '''IFM 99-02:''' Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T; IFM. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15;108(10):3289-94. Epub 2006 Jul 27. [ | + | # '''IFM 99-02:''' Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T; IFM. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15;108(10):3289-94. Epub 2006 Jul 27. [https://doi.org/10.1182/blood-2006-05-022962 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16873668/ PubMed] [https://clinicaltrials.gov/study/NCT00222053 NCT00222053] |
− | ## ''' | + | ## '''Pooled update:''' Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. [https://doi.org/10.1200/jco.2009.25.6081 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834471/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20085933/ PubMed] |
− | # '''**RETRACTED**''' Abdelkefi A, Ladeb S, Torjman L, Othman TB, Lakhal A, Romdhane NB, Omri HE, Elloumi M, Belaaj H, Jeddi R, Aissaouï L, Ksouri H, Hassen AB, Msadek F, Saad A, Hsaïri M, Boukef K, Amouri A, Louzir H, Dellagi K, Abdeladhim AB; Tunisian Multiple Myeloma Study Group. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood. 2008 Feb 15;111(4):1805-10. Epub 2007 Sep 17. [ | + | # '''**RETRACTED**''' Abdelkefi A, Ladeb S, Torjman L, Othman TB, Lakhal A, Romdhane NB, Omri HE, Elloumi M, Belaaj H, Jeddi R, Aissaouï L, Ksouri H, Hassen AB, Msadek F, Saad A, Hsaïri M, Boukef K, Amouri A, Louzir H, Dellagi K, Abdeladhim AB; Tunisian Multiple Myeloma Study Group. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood. 2008 Feb 15;111(4):1805-10. Epub 2007 Sep 17. [https://doi.org/10.1182/blood-2007-07-101212 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17875806/ PubMed] '''**RETRACTED**''' [https://clinicaltrials.gov/study/NCT00207805 NCT00207805] |
<!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. --> | <!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. --> | ||
− | # '''HOVON-50:''' Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [ | + | # '''HOVON-50:''' Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [https://doi.org/10.1182/blood-2009-05-222539 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19880501/ PubMed] [https://clinicaltrials.gov/study/NCT00028886 NCT00028886] |
− | ## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https:// | + | ## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905/ PubMed] |
− | # '''HOVON 49:''' Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. Epub 2010 Jun 1. [ | + | # '''HOVON 49:''' Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. Epub 2010 Jun 1. [https://doi.org/10.1200/jco.2009.26.1610 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20516439/ PubMed] |
− | # '''MRC Myeloma IX:''' Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. [https:// | + | # '''MRC Myeloma IX:''' Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. [https://doi.org/10.1016/S0140-6736(10)62051-X link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21131037/ PubMed] ISRCTN68454111 |
− | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. [ | + | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. [https://doi.org/10.1182/blood-2011-02-338665 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21652683/ PubMed] |
− | ## '''Update:''' Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5;119(1):7-15. Epub 2011 Oct 20. [ | + | ## '''Update:''' Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5;119(1):7-15. Epub 2011 Oct 20. [https://doi.org/10.1182/blood-2011-06-357038 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22021371/ PubMed] |
− | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. [ | + | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. [https://doi.org/10.3324/haematol.2011.043372 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291601/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22058209/ PubMed] |
− | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. [ | + | ## '''Update:''' Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. [https://doi.org/10.1158/1078-0432.CCR-12-3211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23995858/ PubMed] |
− | # '''GEM05/MENOS65:''' Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. [ | + | # '''GEM05/MENOS65:''' Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. [https://doi.org/10.1182/blood-2012-02-408922 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22791289/ PubMed] [https://clinicaltrials.gov/study/NCT00461747 NCT00461747] |
− | ## '''Update:''' Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. [https://doi.org/10.1038/leu.2017.35 link to original article] ''' | + | ## '''Update:''' Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. [https://doi.org/10.1038/leu.2017.35 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28111466/ PubMed] |
− | # '''HOVON-65 | + | # '''HOVON-65:''' Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. [https://doi.org/10.1200/jco.2011.39.6820 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22802322/ PubMed] ISRCTN64455289 |
− | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [ | + | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [https://doi.org/10.1182/blood-2011-09-379164 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22160383/ PubMed] |
− | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https:// | + | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https://doi.org/10.1038/leu.2017.211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28761118/ PubMed] |
− | # ''' | + | # '''GMMG-HD4:''' Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. [https://doi.org/10.1200/jco.2011.39.6820 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22802322/ PubMed] ISRCTN64455289 |
− | # | + | ## '''Subgroup analysis:''' Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. [https://doi.org/10.1182/blood-2011-09-379164 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22160383/ PubMed] |
− | + | ## '''Update:''' Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. [https://doi.org/10.1038/leu.2017.211 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28761118/ PubMed] | |
+ | # '''ECOG E1A06:''' Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, Rajkumar SV. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015 Sep 10;126(11):1294-301. Epub 2015 Jul 8. [https://doi.org/10.1182/blood-2014-12-613927 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26157076/ PubMed] [https://clinicaltrials.gov/study/NCT00602641 NCT00602641] | ||
+ | # '''HOVON87/NMSG18:''' Zweegman S, van der Holt B, Mellqvist UH, Salomo M, Bos GM, Levin MD, Visser-Wisselaar H, Hansson M, van der Velden AW, Deenik W, Gruber A, Coenen JL, Plesner T, Klein SK, Tanis BC, Szatkowski DL, Brouwer RE, Westerman M, Leys MR, Sinnige HA, Haukås E, van der Hem KG, Durian MF, Mattijssen EV, van de Donk NW, Stevens-Kroef MJ, Sonneveld P, Waage A. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 Mar 3;127(9):1109-16. Epub 2016 Jan 22. [https://doi.org/10.1182/blood-2015-11-679415 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26802176/ PubMed] EudraCT 2007-004007-34 | ||
==Thalidomide & Dexamethasone (TD) {{#subobject:3906a8|Regimen=1}}== | ==Thalidomide & Dexamethasone (TD) {{#subobject:3906a8|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TD: '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone | TD: '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone | ||
<br>Thal-Dex: '''<u>Thal</u>'''idomide, '''<u>Dex</u>'''amethasone | <br>Thal-Dex: '''<u>Thal</u>'''idomide, '''<u>Dex</u>'''amethasone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:e146e3|Variant=1}}=== | ===Regimen {{#subobject:e146e3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/ajh.23274 Maiolino et al. 2012 (GBRAM0001)] |
|2003-2008 | |2003-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_2|Dexamethasone]] | |[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_2|Dexamethasone]] | ||
− | |style="background-color:#1a9850"|Superior PFS | + | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 36 vs 19 mo |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous hematopoietic stem cell transplant]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 200 mg PO once per day | *[[Thalidomide (Thalomid)]] 200 mg PO once per day | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 | *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 | ||
− | |||
'''28-day cycle for 12 months or until disease progression''' | '''28-day cycle for 12 months or until disease progression''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''BMT CTN 0102:''' Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; BMT CTN. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. Epub 2011 Sep 29. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611089/ link to PMC article] ''' | + | # '''BMT CTN 0102:''' Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; BMT CTN. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. Epub 2011 Sep 29. [https://doi.org/10.1016/s1470-2045(11)70243-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611089/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21962393/ PubMed] [https://clinicaltrials.gov/study/NCT00075829 NCT00075829] |
<!-- This work was presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, 2008 and at the XII International Myeloma Workshop, Washington, DC, 2009. --> | <!-- This work was presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, 2008 and at the XII International Myeloma Workshop, Washington, DC, 2009. --> | ||
− | # '''GBRAM0001:''' Maiolino A, Hungria VT, Garnica M, Oliveira-Duarte G, Oliveira LC, Mercante DR, Miranda EC, Quero AA, Peres AL, Barros JC, Tanaka P, Magalhães RP, Rego EM, Lorand-Metze I, Lima CS, Renault IZ, Braggio E, Chiattone C, Nucci M, de Souza CA; Brazilian Multiple Myeloma Study Group. Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma. Am J Hematol. 2012 Oct;87(10):948-52. Epub 2012 Jun 23. [https:// | + | # '''GBRAM0001:''' Maiolino A, Hungria VT, Garnica M, Oliveira-Duarte G, Oliveira LC, Mercante DR, Miranda EC, Quero AA, Peres AL, Barros JC, Tanaka P, Magalhães RP, Rego EM, Lorand-Metze I, Lima CS, Renault IZ, Braggio E, Chiattone C, Nucci M, de Souza CA; Brazilian Multiple Myeloma Study Group. Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma. Am J Hematol. 2012 Oct;87(10):948-52. Epub 2012 Jun 23. [https://doi.org/10.1002/ajh.23274 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22730113/ PubMed] [https://clinicaltrials.gov/study/NCT01296503 NCT01296503] |
− | + | ==Thalidomide & Prednisolone (TP) {{#subobject:6f8a22|Regimen=1}}== | |
− | ==Thalidomide & Prednisolone {{#subobject:6f8a22|Regimen=1}}== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:96e048|Variant=1}}=== | ===Regimen {{#subobject:96e048|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2008.18.8573 Spencer et al. 2009 (ALLG MM6)] |
|2002-2005 | |2002-2005 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_historical#Prednisolone_monotherapy|Prednisolone]] | |[[Multiple_myeloma_-_historical#Prednisolone_monotherapy|Prednisolone]] | ||
− | |style="background-color:#1a9850"|Superior OS | + | |style="background-color:#1a9850"|Superior OS<sup>1</sup> (co-primary endpoint)<br>OS60: 66% vs 47%<br>(HR 0.12, 95% CI 0.03-0.56) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2014 update.''<br> | ||
+ | ''Note: Thalidomide dose was increased only if the starting dose was tolerated.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & auto HSCT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Thalidomide (Thalomid)]] 100 mg PO once per day, | + | *[[Thalidomide (Thalomid)]] as follows: |
− | *[[Prednisolone (Millipred)]] 50 mg PO once every other day | + | **Cycle 1: 100 mg PO once per day on days 1 to 14, then 200 mg PO once per day on days 15 to 28 |
− | + | **Cycles 2 to 13: 200 mg PO once per day on days 1 to 28 | |
− | ''' | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisolone (Millipred)]] 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 | |
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
<!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, Orlando, FL, December 9-12, 2006; and at the XIth International Myeloma Workshop, Kos Island, Greece, June 25-30, 2007. --> | <!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, Orlando, FL, December 9-12, 2006; and at the XIth International Myeloma Workshop, Kos Island, Greece, June 25-30, 2007. --> | ||
− | # '''ALLG MM6:''' Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, Gill DS, Horvath N, Reynolds J, Kennedy N. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009 Apr 10;27(11):1788-93. Epub 2009 Mar 9. [ | + | # '''ALLG MM6:''' Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, Gill DS, Horvath N, Reynolds J, Kennedy N. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009 Apr 10;27(11):1788-93. Epub 2009 Mar 9. [https://doi.org/10.1200/jco.2008.18.8573 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19273705/ PubMed] ACTRN12607000382471 |
− | ## '''Subgroup analysis:''' Ho PJ, Brown RD, Spencer A, Jeffels M, Daniher D, Gibson J, Joshua DE. Thalidomide consolidation improves progression-free survival in myeloma with normal but not up-regulated expression of fibroblast growth factor receptor 3: analysis from the Australasian Leukaemia and Lymphoma Group MM6 clinical trial. Leuk Lymphoma. 2012 Sep;53(9):1728-34. Epub 2012 Mar 13. [https:// | + | ## '''Subgroup analysis:''' Ho PJ, Brown RD, Spencer A, Jeffels M, Daniher D, Gibson J, Joshua DE. Thalidomide consolidation improves progression-free survival in myeloma with normal but not up-regulated expression of fibroblast growth factor receptor 3: analysis from the Australasian Leukaemia and Lymphoma Group MM6 clinical trial. Leuk Lymphoma. 2012 Sep;53(9):1728-34. Epub 2012 Mar 13. [https://doi.org/10.3109/10428194.2012.664842 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22329352/ PubMed] |
− | ## '''Update:''' Kalff A, Kennedy N, Smiley A, Prince HM, Roberts AW, Bradstock K, De Abreu Lourenço R, Frampton C, Spencer A. Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study. Lancet Haematol. 2014 Dec;1(3):e112-9. Epub 2014 Dec 1. [https:// | + | ## '''Update:''' Kalff A, Kennedy N, Smiley A, Prince HM, Roberts AW, Bradstock K, De Abreu Lourenço R, Frampton C, Spencer A. Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study. Lancet Haematol. 2014 Dec;1(3):e112-9. Epub 2014 Dec 1. [https://doi.org/10.1016/S2352-3026(14)00022-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27029229/ PubMed] |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
+ | ==Thalidomide & Prednisone (TP) {{#subobject:c74709|Regimen=1}}== | ||
+ | TP: '''<u>T</u>'''halidomide & '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:ff7fc7|Variant=1}}=== | ===Regimen {{#subobject:ff7fc7|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 1,932: | Line 2,512: | ||
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587317/ Stewart et al. 2013 (NCIC CTG MY.10)] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587317/ Stewart et al. 2013 (NCIC-CTG MY.10)] |
|2002-2009 | |2002-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | |[[Multiple_myeloma_-_null_regimens#Observation|Observation]] | ||
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS48: 68% vs 60%<br>(HR 0.77) |
− | |style="background-color:# | + | | style="background-color:#d73027" |Decreased QOL |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan with autologous HSCT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Thalidomide (Thalomid)]] 200 mg PO once per day | + | *[[Thalidomide (Thalomid)]] 200 mg PO once per day |
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 50 mg PO once every other day | *[[Prednisone (Sterapred)]] 50 mg PO once every other day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*"[[:Category:Bisphosphonates|Bisphosphonates]], histamine-2 blockers, and laxatives were recommended" | *"[[:Category:Bisphosphonates|Bisphosphonates]], histamine-2 blockers, and laxatives were recommended" | ||
*"Anticoagulant and antiplatelet medications were not mandated" | *"Anticoagulant and antiplatelet medications were not mandated" | ||
− | |||
'''Four years or until disease progression''' | '''Four years or until disease progression''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''NCIC CTG MY.10:''' Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. Epub 2013 Jan 7. [ | + | # '''NCIC-CTG MY.10:''' Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. Epub 2013 Jan 7. [https://doi.org/10.1182/blood-2012-09-451872 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23297129/ PubMed] [https://clinicaltrials.gov/study/NCT00049673 NCT00049673] |
− | ==Bortezomib & | + | ==Bortezomib & Prednisone (VP) {{#subobject:ee2988|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
VP: '''<u>V</u>'''elcade (Bortezomib) & '''<u>P</u>'''rednisone | VP: '''<u>V</u>'''elcade (Bortezomib) & '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:763da1|Variant=1}}=== | ===Regimen {{#subobject:763da1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(10)70187-X Mateos et al. 2010 (GEM2005)] |
|2006-2008 | |2006-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#VT|VT]] | |[[#VT|VT]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
− | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VMP|VMP]] x 6 versus [[Multiple_myeloma,_induction#VTP|VTP]] x 6 | + | *Induction [[Multiple_myeloma,_induction#VMP|VMP]] x 6 versus [[Multiple_myeloma,_induction#VTP|VTP]] x 6 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 50 mg PO once every other day | *[[Prednisone (Sterapred)]] 50 mg PO once every other day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Patients with bone disease received [[:Category:Bisphosphonates|bisphosphonates]] | *Patients with bone disease received [[:Category:Bisphosphonates|bisphosphonates]] | ||
*Prophylactic [[Acyclovir (Zovirax)]] was recommended. | *Prophylactic [[Acyclovir (Zovirax)]] was recommended. | ||
− | |||
'''3-month cycle for up to 12 cycles (3 years)''' | '''3-month cycle for up to 12 cycles (3 years)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''GEM2005:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. [https:// | + | # '''GEM2005:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. [https://doi.org/10.1016/S1470-2045(10)70187-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20739218/ PubMed] [https://clinicaltrials.gov/study/NCT00443235 NCT00443235] |
− | ## '''Subgroup analysis:''' Mateos MV, Gutiérrez NC, Martín-Ramos ML, Paiva B, Montalbán MA, Oriol A, Martínez-López J, Teruel AI, Bengoechea E, Martín A, Díaz-Mediavilla J, de Arriba F, Palomera L, Hernández JM, Sureda A, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, Fernández M, García-Sanz R, Vidriales MB, Bladé J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. Epub 2011 Sep 6. [ | + | ## '''Subgroup analysis:''' Mateos MV, Gutiérrez NC, Martín-Ramos ML, Paiva B, Montalbán MA, Oriol A, Martínez-López J, Teruel AI, Bengoechea E, Martín A, Díaz-Mediavilla J, de Arriba F, Palomera L, Hernández JM, Sureda A, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, Fernández M, García-Sanz R, Vidriales MB, Bladé J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. Epub 2011 Sep 6. [https://doi.org/10.1182/blood-2011-04-345801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21900193/ PubMed] |
− | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. Epub 2012 Aug 13. [ | + | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. Epub 2012 Aug 13. [https://doi.org/10.1182/blood-2012-05-427815 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22889759/ PubMed] |
− | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?. Blood. 2014 Sep 18;124(12):1887-93. Epub 2014 Aug 7. [ | + | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?. Blood. 2014 Sep 18;124(12):1887-93. Epub 2014 Aug 7. [https://doi.org/10.1182/blood-2014-05-573733 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25102853/ PubMed] |
− | |||
==VT {{#subobject:e94510|Regimen=1}}== | ==VT {{#subobject:e94510|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
VT: '''<u>V</u>'''elcade (Bortezomib) & '''<u>T</u>'''halidomide | VT: '''<u>V</u>'''elcade (Bortezomib) & '''<u>T</u>'''halidomide | ||
<br>TV: '''<u>T</u>'''halidomide & '''<u>V</u>'''elcade (Bortezomib) | <br>TV: '''<u>T</u>'''halidomide & '''<u>V</u>'''elcade (Bortezomib) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 1.3/50 x 2 y {{#subobject:8a32ae|Variant=1}}=== | ===Regimen variant #1, 1.3/50 x 2 y {{#subobject:8a32ae|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2010.29.8216 Palumbo et al. 2010 (GIMEMA MM-03-05)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2006-2009 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VMPT|VMPT]] x 9 | + | *Induction [[Multiple_myeloma,_induction#VMPT|VMPT]] x 9 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once on day 1 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once on day 1 | ||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day | ||
− | |||
'''14-day cycle for up to 2 years or until disease progression or relapse''' | '''14-day cycle for up to 2 years or until disease progression or relapse''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 1.3/50 x 3 y {{#subobject:8eb947|Variant=1}}=== | ===Regimen variant #2, 1.3/50 x 3 y {{#subobject:8eb947|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(10)70187-X Mateos et al. 2010 (GEM2005)] |
|2006-2008 | |2006-2008 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[# | + | |[[#Bortezomib_.26_Prednisone_.28VP.29|VP]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Multiple_myeloma,_induction#VMP|VMP]] x 6 versus [[Multiple_myeloma,_induction#VTP|VTP]] x 6 | + | *Induction [[Multiple_myeloma,_induction#VMP|VMP]] x 6 versus [[Multiple_myeloma,_induction#VTP|VTP]] x 6 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
*[[Thalidomide (Thalomid)]] 50 mg PO once per day | *[[Thalidomide (Thalomid)]] 50 mg PO once per day | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Patients with bone disease received [[:Category:Bisphosphonates|bisphosphonates]] | *Patients with bone disease received [[:Category:Bisphosphonates|bisphosphonates]] | ||
*Prophylactic [[Acyclovir (Zovirax)|aciclovir]] was recommended. | *Prophylactic [[Acyclovir (Zovirax)|aciclovir]] was recommended. | ||
*Thromboprophylaxis with either [[aspirin]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]] | *Thromboprophylaxis with either [[aspirin]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]] | ||
− | |||
'''3-month cycle for up to 12 cycles (3 years)''' | '''3-month cycle for up to 12 cycles (3 years)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1.3/100 {{#subobject:61320d|Variant=1}}=== | ===Regimen variant #3, 1.3/100 {{#subobject:61320d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2012-02-408922 Rosiñol et al. 2012 (GEM05/MENOS65)] |
|2006-2009 | |2006-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |1. [[Multiple_myeloma_-_historical#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]]<br> 2. [[#Thalidomide_monotherapy|Thalidomide]] | + | |1. [[Multiple_myeloma_-_historical#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]]<br>2. [[#Thalidomide_monotherapy|Thalidomide]] |
− | |style="background-color:#91cf60"|Seems to have superior PFS ( | + | |style="background-color:#91cf60"|Seems to have superior PFS<sup>1</sup> (secondary endpoint) |
|- | |- | ||
|} | |} | ||
− | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment | + | ''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br> |
+ | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Melphalan_monotherapy.2C_then_auto_HSCT|High-dose melphalan & autologous HCT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11 | ||
*[[Thalidomide (Thalomid)]] 100 mg PO once per day | *[[Thalidomide (Thalomid)]] 100 mg PO once per day | ||
− | |||
'''3-month cycle for up to 12 cycles (3 years)''' | '''3-month cycle for up to 12 cycles (3 years)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''GEM2005:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. [https:// | + | # '''GEM2005:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. [https://doi.org/10.1016/S1470-2045(10)70187-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20739218/ PubMed] [https://clinicaltrials.gov/study/NCT00443235 NCT00443235] |
− | ## '''Subgroup analysis:''' Mateos MV, Gutiérrez NC, Martín-Ramos ML, Paiva B, Montalbán MA, Oriol A, Martínez-López J, Teruel AI, Bengoechea E, Martín A, Díaz-Mediavilla J, de Arriba F, Palomera L, Hernández JM, Sureda A, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, Fernández M, García-Sanz R, Vidriales MB, Bladé J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. Epub 2011 Sep 6. [ | + | ## '''Subgroup analysis:''' Mateos MV, Gutiérrez NC, Martín-Ramos ML, Paiva B, Montalbán MA, Oriol A, Martínez-López J, Teruel AI, Bengoechea E, Martín A, Díaz-Mediavilla J, de Arriba F, Palomera L, Hernández JM, Sureda A, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, Fernández M, García-Sanz R, Vidriales MB, Bladé J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. Epub 2011 Sep 6. [https://doi.org/10.1182/blood-2011-04-345801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21900193/ PubMed] |
− | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. Epub 2012 Aug 13. [ | + | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. Epub 2012 Aug 13. [https://doi.org/10.1182/blood-2012-05-427815 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22889759/ PubMed] |
− | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?. Blood. 2014 Sep 18;124(12):1887-93. Epub 2014 Aug 7. [ | + | ## '''Update:''' Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?. Blood. 2014 Sep 18;124(12):1887-93. Epub 2014 Aug 7. [https://doi.org/10.1182/blood-2014-05-573733 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25102853/ PubMed] |
− | # '''GIMEMA MM-03-05:''' Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. [ | + | # '''GIMEMA MM-03-05:''' Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. [https://doi.org/10.1200/jco.2010.29.8216 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20940200/ PubMed] [https://clinicaltrials.gov/study/NCT01063179 NCT01063179] |
− | ## '''Post-hoc analysis:''' Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. [ | + | ## '''Post-hoc analysis:''' Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. [https://doi.org/10.1182/blood-2010-07-294983 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20807892/ PubMed] |
− | ## '''Subgroup analysis:''' | + | ## '''Subgroup analysis:''' Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.31.6844 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21282540/ PubMed] |
− | ## ''' | + | ## '''Subgroup analysis:''' Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. Epub 2011 Sep 27. [https://doi.org/10.1182/blood-2011-05-353995 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21951682/ PubMed] |
− | # ''' | + | ## '''Update:''' Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014 Mar 1;32(7):634-40. Epub 2014 Jan 21. [https://doi.org/10.1200/jco.2013.52.0023 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24449241/ PubMed] |
− | + | # '''GEM05/MENOS65:''' Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. [https://doi.org/10.1182/blood-2012-02-408922 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22791289/ PubMed] [https://clinicaltrials.gov/study/NCT00461747 NCT00461747] | |
− | + | ## '''Update:''' Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. [https://doi.org/10.1038/leu.2017.35 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28111466/ PubMed] | |
<section end=1st-consol /> | <section end=1st-consol /> | ||
{{#lst:Multiple myeloma|bottom}} | {{#lst:Multiple myeloma|bottom}} |
Latest revision as of 23:39, 15 July 2024
Section editor | |
---|---|
Samuel M. Rubinstein, MD University of North Carolina Chapel Hill, NC, USA |
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. If you still can't find it, please let us know so we can add it!.
Note: due to its size/complexity, multiple myeloma has been split into sub-pages:
- Induction (transplant eligible and ineligible)
- First-line consolidation and maintenance [this page]
- Relapsed/refractory, including subsequent consolidation and maintenance
- Smoldering multiple myeloma
30 regimens on this page
71 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO/CCO
- 2019: Mikhael et al. Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline PubMed
- 2018: Anderson et al. Role of bone-modifying agents in multiple myeloma: American Society of Clinical Oncology Clinical Practice Guideline update PubMed
BSH/UKMF
- 2017: Guidelines for the use of imaging in the management of patients with myeloma PubMed
- 2017: Guidelines for screening and management of late and long-term consequences of myeloma and its treatment PubMed
- 2014: Updates to the guidelines for the diagnosis and management of multiple myeloma PubMed
European Myeloma Network (EMN)
- 2020: Ludwig et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network PubMed
- 2018: Caers et al. European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when PubMed
- 2018: Gay et al. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives PubMed
EHA/ESMO
- 2021: Dimopoulos et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2017: Moreau et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2013: Moreau et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Harousseau & Dreyling. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Harousseau & Dreyling. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Harousseau & Dreyling. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Harousseau. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Harousseau et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of multiple myeloma PubMed
IMWG
- 2021: Moreau et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group PubMed
- 2021: Terpos et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group PubMed
- 2016: Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group PubMed
- 2016: International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment PubMed
- 2014: International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation PubMed
- 2013: International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease PubMed
NCCN
- NCCN Guidelines - Multiple Myeloma
- 2020: Kumar et al. Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2017: Kumar et al. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2016: Anderson et al. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016 PubMed
- 2015: Anderson et al. Multiple Myeloma, Version 2.2016: Clinical Practice Guidelines in Oncology PubMed
- 2011: Anderson et al. Multiple myeloma. PubMed
- 2009: Anderson et al. NCCN clinical practice guidelines in oncology: multiple myeloma. PubMed
- 2007: Anderson et al. Multiple myeloma. Clinical practice guidelines in oncology. PubMed
- 2004: Anderson et al. Multiple myeloma clinical practice guidelines in oncoloqy. PubMed
SITC
- 2020: Shah et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma PubMed
Consolidation after first-line therapy
Note that there is no crisp distinction between consolidation and maintenance. Generally regimens that are intended for a long or indefinite duration would be considered maintenance, whereas regimens with a short intended course would be considered consolidation.
Bortezomib monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mellqvist et al. 2013 (NMSG 15/05) | 2005-2009 | Phase 3 (E-esc) | Observation | Might have superior PFS (primary endpoint) |
This trial only included bortezomib-naive patients; induction regimen was not specified but the majority received Cy-Dex.
Preceding treatment
- All patients underwent autologous hematopoietic cell transplant consolidation at least 3 months prior to starting bortezomib consolidation.
Targeted therapy
- Bortezomib (Velcade) as follows:
- Cycles 1 & 2: 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Cycles 3 to 6: 1.3 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy
- Bisphosphonates were administered "according to national guidelines."
21-day cycle for 2 cycles, then 28-day cycle for 4 cycles
Regimen variant #2, 4 out of 5 weeks for 20 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Einsele et al. 2017 (MMY-3012) | 2006-2013 | Phase 3 (E-esc) | Observation | Seems to have superior PFS1 Median PFS: 33.6 vs 27.8 mo (HR 0.75, 95% CI 0.59-0.97) |
Einsele et al. 2017 (MMY-3013) | 2006-2013 | Phase 3 (E-esc) | Observation | Seems to have superior PFS1 Median PFS: 33.6 vs 27.8 mo (HR 0.75, 95% CI 0.59-0.97) |
1Reported efficacy is based on the combined analysis.
Targeted therapy
- Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15, 22
35-day cycle for 4 cycles
Regimen variant #3, 4 out of 5 weeks for 25 weeks
Study | Dates of enrollment | Evidence |
---|---|---|
Niesvizky et al. 2015 (UPFRONT) | 2007-2010 | Non-randomized part of phase 3b RCT |
Targeted therapy
- Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15, 22
35-day cycle for 5 cycles
Regimen variant #4, 4 out of 6 weeks for 24 weeks
Study | Dates of enrollment | Evidence |
---|---|---|
Kumar et al. 2012 (EVOLUTION) | 2008-2009 | Non-randomized part of phase 2 RCT |
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive therapy
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
42-day cycle for 4 cycles
References
- EVOLUTION: Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00507442
- NMSG 15/05: Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. Epub 2013 Apr 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00417911
- UPFRONT: Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol. 2015 Nov 20;33(33):3921-9. Epub 2015 Jun 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00507416
- MMY-3012: Einsele H, Knop S, Vogel M, Müller J, Kropff M, Metzner B, Langer C, Sayer H, Jung W, Dürk HA, Salwender H, Wandt H, Bassermann F, Gramatzki M, Rösler W, Wolf HH, Brugger W, Engelhardt M, Fischer T, Liebisch P, Straka C. Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma. Leukemia. 2017 Jun;31(6):1463-1466. Epub 2017 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00416273
- MMY-3013: Einsele H, Knop S, Vogel M, Müller J, Kropff M, Metzner B, Langer C, Sayer H, Jung W, Dürk HA, Salwender H, Wandt H, Bassermann F, Gramatzki M, Rösler W, Wolf HH, Brugger W, Engelhardt M, Fischer T, Liebisch P, Straka C. Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma. Leukemia. 2017 Jun;31(6):1463-1466. Epub 2017 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00416208
Bortezomib & Melphalan, then auto HSCT
Bor-HDM: Bortezomib, High Dose Melphalan
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Roussel et al. 2009 | 2007-07 to 2007-12 | Phase 2 |
Targeted therapy
- Bortezomib (Velcade) 1 mg/m2 IV once per day on days -6, -3, +1, +4
Chemotherapy
- Melphalan (Alkeran) 100 mg/m2 IV once per day on days -2 & -1
- Roussel et al. 2009 gave as a single 200 mg/m2 dose on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00642395
DCEP
DCEP: Dexamethasone, Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Harousseau et al. 2010 (IFM 2005-01) | 2005-2008 | Phase 3 (E-esc) | Observation | Did not meet composite primary endpoint of CR/nCR rate |
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 400 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m2)
- Etoposide (Vepesid) 40 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m2)
- Cisplatin (Platinol) 15 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 60 mg/m2)
28-day cycle for 2 cycles
Subsequent treatment
References
- IFM 2005-01: Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20;28(30):4621-9. Epub 2010 Sep 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00200681
KTD
KTD: Kyprolis (Carfilzomib), Thalidomide, Dexamethasone
Regimen variant #1, 27/50/20
Study | Dates of enrollment | Evidence |
---|---|---|
Sonneveld et al. 2014 (CARTHADEX) | 2010-2013 | Phase 2 |
Note: this was the dosing for Cohort 1.
Preceding treatment
- High-dose melphalan with stem cell rescue consolidation
Targeted therapy
- Carfilzomib (Kyprolis) 27 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Thalidomide (Thalomid) 50 mg PO once per day
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22
28-day cycle for 4 cycles
Regimen variant #2, 36/50/20
Study | Dates of enrollment | Evidence |
---|---|---|
Sonneveld et al. 2014 (CARTHADEX) | 2010-2013 | Phase 2 |
Note: this was the dosing for Cohort 2.
Preceding treatment
- High-dose melphalan with stem cell rescue consolidation
Targeted therapy
- Carfilzomib (Kyprolis) 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Thalidomide (Thalomid) 50 mg PO once per day
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22
28-day cycle for 4 cycles
References
- CARTHADEX: Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NTR2422
Melphalan monotherapy, then auto HSCT
HDM: High-Dose Melphalan
Synopsis
Development
The concept of high-dose chemotherapy followed by ASCT emerged as a treatment modality for hematological malignancies in the 1980s. The rationale was to provide high doses of chemotherapy to eradicate malignant cells that were resistant to conventional doses. However, these high doses also destroyed the patient's bone marrow, necessitating a rescue with previously harvested and stored stem cells. Autologous transplantation uses the patient's own stem cells, harvested prior to the high-dose chemotherapy.
Clinical Trials & Evidence
[1] Attal et al., 1996 (Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New England Journal of Medicine. 1996;335:91-7): In this landmark trial, patients with multiple myeloma were randomized to receive either standard chemotherapy or high-dose chemotherapy followed by ASCT. The results showed a higher response rate and prolonged event-free survival in the ASCT group.
[2] Barlogie et al., 1999 (Barlogie B, Jagannath S, Vesole DH, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1999;93:1172-9): This study demonstrated the benefit of two consecutive ASCTs (tandem transplants) over a single transplant in patients with newly diagnosed multiple myeloma.
2000s-2010s Trials: Further studies over these years demonstrated the sustained benefit of ASCT in multiple myeloma, especially when combined with novel agents like proteasome inhibitors, immunomodulatory agents, CD38 monoclonal antibodies, and corticosteroids.
Application in the Modern Era
1. Induction Therapy: Before ASCT, patients receive induction therapy with a combination of drugs for cytoreduction. Modern regimens often include monoclonal antibodies (e.g., daratumumab), proteasome inhibitors (e.g., bortezomib or carfilzomib), immunomodulatory drugs (e.g., lenalidomide), and steroids (typically dexamethasone).
2. Stem Cell Harvesting: Stem cells are collected from the patient’s peripheral blood after mobilization with growth factors, usually granulocyte colony-stimulating factor (G-CSF) often in combination with plerixafor.
3. High-Dose Chemotherapy: Melphalan remains the standard conditioning agent for multiple myeloma. Patients receive high doses of melphalan, which kill myeloma cells but also suppress the bone marrow.
4. Stem Cell Infusion: After chemotherapy, the previously harvested stem cells are infused back into the patient to "rescue" the bone marrow.
5. Maintenance Therapy: Following recovery from ASCT, patients often receive maintenance therapy with agents like lenalidomide to prolong remission.
Conclusion
High-dose chemotherapy followed by ASCT has significantly improved outcomes for patients with multiple myeloma over the past few decades. While newer therapies continue to emerge, ASCT remains an integral part of the treatment paradigm for eligible patients.
The draft for this synopsis was generated by a large language model and then manually edited by the page editor for accuracy and style. See this page for more information about this pilot project.
Regimen variant #1, 140 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Barlogie et al. 1986 | Not reported | Non-randomized, fewer than 20 pts |
Chemotherapy
- Melphalan (Alkeran) 70 mg/m2 IV once per day on days -2 & -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, 200 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bladé et al. 2005 | 1994-1999 | Phase 3 (E-esc) | VBMCP/VBAD | Did not meet efficacy endpoint |
Moreau et al. 2002 (IFM 9502) | 1995-1999 | Phase 3 (E-de-esc) | Melphalan & TBI, then auto HSCT | Did not meet primary endpoint of CR rate |
Cavo et al. 2007 (Bologna 96) | 1996-2001 | Phase 3 (C) | Melphalan, then auto HSCT, then Melphalan & Busulfan, then auto HSCT | Inferior EFS |
Mai et al. 2016 (GMMG-HD2) | 1998-2002 | Phase 3 (C) | Tandem melphalan, then auto HSCT | Non-inferior EFS |
Lokhorst et al. 2009 (HOVON-50) | 2001-2005 | Non-randomized part of phase 3 RCT | ||
Björkstrand et al. 2011 (EBMT-NMAM2000) | 2001-2005 | Phase 3 (C) | MEL200, then auto HSCT, then RIC allo HSCT | Seems to have inferior OS |
Morgan et al. 2010 (MRC Myeloma IX) | 2003-2007 | Non-randomized part of phase 3 RCT | ||
Sonneveld et al. 2012 (HOVON-65) | 2005-2008 | Non-randomized part of phase 3 RCT | ||
Rosiñol et al. 2012 (GEM05/MENOS65) | 2006-2009 | Non-randomized part of phase 3 RCT | ||
Moreau et al. 2011 (IFM 2007-02) | 2008-03 to 2009-01 | Non-randomized part of phase 3 RCT | ||
Roussel et al. 2014 (IFM 2008) | 2009 | Phase 2 | ||
Mai et al. 2015 (GMMG-MM5) | 2010-2012 | Non-randomized part of phase 3 RCT | ||
Attal et al. 2017 (IFM 2009) | 2010-2012 | Phase 3 (C) | RVD consolidation | Superior PFS Median PFS: 50 vs 36 mo (HR 0.65, 95% CI 0.53-0.80) |
Sonneveld et al. 2014 (CARTHADEX) | 2010-2013 | Phase 2 | ||
Stadtmauer et al. 2019 (STAMINA) | 2010-2013 | Phase 3 (C) | 1. Tandem melphalan, then auto HSCT 2. MEL200, then auto HSCT, then RVD consolidation |
Did not meet primary endpoint of PFS38 |
Richardson et al. 2022 (DETERMINATION) | 2010-10-01 to 2018-01-30 | Phase 3 (C) | RVD consolidation | Superior PFS (primary endpoint) Median PFS: 67.5 vs 46.2 mo (HR 0.65, 95% CI 0.52-0.81) |
Lok et al. 2014 | 2011-2013 | Non-randomized | ||
Bashir et al. 2019 (MDACC 2010-0071) | 2011-2017 | Phase 3 (C) | Bu/Mel, then auto HSCT | Seems to have inferior PFS |
Roussel et al. 2022 (IFM 2014-02) | 2015-01-21 to 2016-09-21 | Phase 3 (C) | Bor-HDM, then auto HSCT | Did not meet composite primary endpoint of sCR/CR rate at day +60 |
Preceding treatment
- IFM 9502: Induction VAD x 3
- Bladé et al. 2005: Induction VBMCP/VBAD x 4
- Bologna 96: Induction VAD x 4
- HOVON-50: Induction TAD x 3 versus VAD x 3
- IFM 2007-02: Induction vtD x 4 versus Vd x 4
- MRC Myeloma IX: Induction CTD x 4 to 6 versus CVAD x 4 to 6
- GEM05/MENOS65: Induction TD x 6 versus VBMCP/VBAD/B x 6 versus VTD x 6
- HOVON-65: Induction PAD x 3 versus VAD x 3
- Lok et al. 2014: Induction vtD x 4
- IFM 2008: Induction RVD x 3
- CARTHADEX: Induction KTD x 4
- GMMG-MM5: Induction VCD x 3 versus PAd x 3
- IFM 2009 & DETERMINATION: Induction RVD x 3
- IFM 2014-02: Induction VTd or CyBorD or RVd
Chemotherapy
- Melphalan (Alkeran) 200 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Subsequent treatment
- IFM 9502: Interferon alfa maintenance x 12 mo
- Bladé et al. 2005: IFN & Dexamethasone maintenance
- Bologna 96: Interferon alfa maintenance
- HOVON-50, induced with VAD: Interferon alfa maintenance
- HOVON-50, induced with TAD: Thalidomide maintenance
- MRC Myeloma IX: Thalidomide maintenance versus no further treatment
- GEM05/MENOS65: Interferon alfa-2b maintenance x 36 mo versus Thalidomide x 36 mo versus TV x 36 mo
- HOVON-65, induced with PAD: Bortezomib maintenance x 24 mo
- HOVON-65, induced with VAD: Thalidomide maintenance x 24 mo
- Lok et al. 2014 & IFM 2014-02: vtD consolidation x 2
- IFM 2008 & IFM 2009: RVD consolidation x 2
- CARTHADEX: KTD consolidation x 4
- GMMG-MM5, if at least nCR not achieved: MEL200, then auto HSCT
- GMMG-MM5, at least nCR achieved: Lenalidomide maintenance x 24 mo vs Lenalidomide until CR
- DETERMINATION: Lenalidomide maintenance
References
- Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. link to original article dosing details in abstract have been reviewed by our editors PubMed
- IFM 9502: Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, François S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL; Intergroupe Francophone du Myélome. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002 Feb 1;99(3):731-5. link to original article PubMed
- Bladé J, Rosiñol L, Sureda A, Ribera JM, Díaz-Mediavilla J, García-Laraña J, Mateos MV, Palomera L, Fernández-Calvo J, Martí JM, Giraldo P, Carbonell F, Callís M, Trujillo J, Gardella S, Moro MJ, Barez A, Soler A, Font L, Fontanillas M, San Miguel J; PETHEMA. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005 Dec 1;106(12):3755-9. Epub 2005 Aug 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Bologna 96: Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, Di Raimondo F, Volpe E, Ronconi S, Cangini D, Narni F, Carubelli A, Masini L, Catalano L, Fiacchini M, de Vivo A, Gozzetti A, Lazzaro A, Tura S, Baccarani M. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007 Jun 10;25(17):2434-41. Epub 2007 May 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00378222
- HOVON-50: Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; HOVON. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00028886
- Update: van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. link to original article PubMed
- MRC Myeloma IX: Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. link to original article link to PMC article PubMed ISRCTN68454111
- Update: Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5;119(1):7-15. Epub 2011 Oct 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. link to original article PubMed
- EBMT-NMAM2000: Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. link to original article PubMed
- IFM 2007-02: Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00910897
- GEM05/MENOS65: Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00461747
- Update: Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- HOVON-65: Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN64455289
- Subgroup analysis: Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. link to original article PubMed
- Update: Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. link to original article PubMed
- Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous bortezomib incorporated into the bortezomib-thalidomide-dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- IFM 2008: Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01206205
- CARTHADEX: Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NTR2422
- GMMG-MM5: Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, Munder M, Jauch A, Schurich B, Hielscher T, Merz M, Huegle-Doerr B, Seckinger A, Hose D, Hillengass J, Raab MS, Neben K, Lindemann HW, Zeis M, Gerecke C, Schmidt-Wolf IG, Weisel K, Scheid C, Salwender H, Goldschmidt H. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015 Aug;29(8):1721-9. Epub 2015 Mar 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2010-019173-16
- Subgroup analysis: Merz M, Salwender H, Haenel M, Mai EK, Bertsch U, Kunz C, Hielscher T, Blau IW, Scheid C, Hose D, Seckinger A, Jauch A, Hillengass J, Raab MS, Schurich B, Munder M, Schmidt-Wolf IG, Gerecke C, Lindemann HW, Zeis M, Weisel K, Duerig J, Goldschmidt H. Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial. Haematologica. 2015 Jul;100(7):964-9. Epub 2015 Apr 3. link to original article link to PMC article PubMed
- Update: Goldschmidt H, Mai EK, Dürig J, Scheid C, Weisel KC, Kunz C, Bertsch U, Hielscher T, Merz M, Munder M, Lindemann HW, Hügle-Dörr B, Tichy D, Giesen N, Hose D, Seckinger A, Huhn S, Luntz S, Jauch A, Elmaagacli A, Rabold B, Fuhrmann S, Brossart P, Goerner M, Bernhard H, Hoffmann M, Hillengass J, Raab MS, Blau IW, Hänel M, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG). Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. Leukemia. 2020 Jul;34(7):1853-1865. Epub 2020 Feb 7. link to original article PubMed
- GMMG-HD2: Mai EK, Benner A, Bertsch U, Brossart P, Hänel A, Kunzmann V, Naumann R, Neben K, Egerer G, Ho AD, Hillengass J, Raab MS, Neubauer A, Peyn A, Ko YD, Peter N, Scheid C, Goldschmidt H. Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial. Br J Haematol. 2016 Jun;173(5):731-41. Epub 2016 Mar 17. link to original article PubMed DRKS00008864
- IFM 2009: Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01191060
- STAMINA: Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, Efebera Y, Ganguly S, Gasparetto C, Geller N, Horowitz MM, Koreth J, Knust K, Landau H, Brunstein C, McCarthy P, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Giralt S, Somlo G, Krishnan A. Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial. J Clin Oncol. 2019 Mar 1;37(7):589-597. Epub 2019 Jan 17. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT01109004
- MDACC 2010-0071: Bashir Q, Thall PF, Milton DR, Fox PS, Kawedia JD, Kebriaei P, Shah N, Patel K, Andersson BS, Nieto YL, Valdez BC, Parmar S, Rondon G, Delgado R, Hosing C, Popat UR, Oran B, Ciurea SO, Lin P, Weber DM, Thomas SK, Lee HC, Manasanch EE, Orlowski RZ, Williams LA, Champlin RE, Qazilbash MH. Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial. Lancet Haematol. 2019 May;6(5):e266-e275. Epub 2019 Mar 22. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT01413178
- EMN02/HOVON-95: Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. link to original article PubMed NCT01208766
- Update: Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. link to original article PubMed
- IFM 2014-02: Roussel M, Lauwers-Cances V, Macro M, Leleu X, Royer B, Hulin C, Karlin L, Perrot A, Touzeau C, Chrétien ML, Rigaudeau S, Dib M, Nicolas-Virelizier E, Escoffre-Barbe M, Belhadj K, Mariette C, Stoppa AM, Araujo C, Doyen C, Fontan J, Kolb B, Garderet L, Brechignac S, Malfuson JV, Jaccard A, Lenain P, Borel C, Hebraud B, Benbrahim O, Dorvaux V, Manier S, Augeul-Meunier K, Vekemans MC, Randriamalala E, Chaoui D, Caers J, Chaleteix C, Benboubker L, Vincent L, Glaisner S, Zunic P, Slama B, Eveillard JR, Humbrecht-Kraut C, Morel V, Mineur P, Eisenmann JC, Demarquette H, Richez V, Vignon M, Caillot D, Facon T, Moreau P, Colin AL, Olivier P, Wuilleme S, Avet-Loiseau H, Corre J, Attal M. Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study. Blood. 2022 May 5;139(18):2747-2757. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02197221
- DETERMINATION: Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. Epub 2022 Jun 5. link to original article link to PMC article PubMed NCT01208662
MPR
MPR: Melphalan, Prednisone, Revlimid (Lenalidomide)
Regimen variant #1, 0.18/2/10
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Palumbo et al. 2014 (MPRvsMEL200) | 2007-2009 | Phase 3 (C) | Tandem Melphalan, then auto HSCT | Seems to have inferior OS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Preceding treatment
- Rd induction x 4
Chemotherapy
- Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4
Glucocorticoid therapy
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycle for 6 cycles
Subsequent treatment
- Lenalidomide maintenance versus no further treatment
Regimen variant #2, 2/50/10
Study | Dates of enrollment | Evidence |
---|---|---|
Falco et al. 2012 | 2008-2009 | Phase 2 |
Note: this is a component of the sequential "RP-MPR-RP" protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- RP induction x 4
Chemotherapy
- Melphalan (Alkeran) 2 mg PO three times per week
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO three times per week
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Supportive therapy
- Thromboprophylaxis: Aspirin 100 mg PO once per day, taken during lenalidomide treatment (unclear from protocol if this also means off weeks)
- Antiviral prophylaxis if history of VZV.
28-day cycle for 6 cycles
Subsequent treatment
- RP maintenance
Regimen variant #3, 2/50/15
Study | Dates of enrollment | Evidence |
---|---|---|
Falco et al. 2012 | 2008-2009 | Phase 2 |
Note: this is a component of the sequential "RP-MPR-RP" protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- RP induction x 4
Chemotherapy
- Melphalan (Alkeran) 2 mg PO three times per week
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO three times per week
Targeted therapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Supportive therapy
- Thromboprophylaxis: Aspirin 100 mg PO once per day, taken during lenalidomide treatment (unclear from protocol if this also means off weeks)
- Antiviral prophylaxis if history of VZV.
28-day cycle for 6 cycles
Subsequent treatment
- RP maintenance
References
- Falco P, Cavallo F, Larocca A, Rossi D, Guglielmelli T, Rocci A, Grasso M, Siez ML, De Paoli L, Oliva S, Molica S, Mina R, Gay F, Benevolo G, Musto P, Omedè P, Freilone R, Bringhen S, Carella AM, Gaidano G, Boccadoro M, Palumbo A. Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. 2013 Mar;27(3):695-701. Epub 2012 Sep 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- MPRvsMEL200: Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00551928
Lenalidomide & Prednisone (RP)
RP: Revlimid (Lenalidomide) & Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Palumbo et al. 2010 | 2005-2007 | Phase 2 |
Preceding treatment
- Tandem MEL-100, then auto HSCT consolidation
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO once every other day
Supportive therapy
- Aspirin 100 mg PO once per day during lenalidomide treatment
28-day cycle for 4 cycles
Subsequent treatment
- Lenalidomide maintenance
References
- Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2005-004714-32
- Update: Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. link to original article dosing details in abstract have been reviewed by our editors PubMed
RVD
RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
VDR: Velcade (Bortezomib), Dexamethasone, Revlimid (Lenalidomide)
VRD: Velcade (Bortezomib), Revlimid (Lenalidomide), Dexamethasone
VRd: Velcade (Bortezomib), Revlimid (Lenalidomide), low-dose dexamethasone
Regimen variant #1, 2 cycles post-transplant with lower-dose dex
Study | Dates of enrollment | Evidence |
---|---|---|
Attal et al. 2017 (IFM 2009) | 2010-2012 | Non-randomized part of phase 3 RCT |
Preceding treatment
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Dexamethasone (Decadron) 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycle for 2 cycles
Subsequent treatment
- Lenalidomide maintenance
Regimen variant #2, 2 cycles with intermediate-dose dex
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cavo et al. 2020 (EMN02/HOVON-95) | 2011-2014 | Phase 3 (E-esc) | No further consolidation | Seems to have superior PFS1 (primary endpoint) Median PFS: 59.3 vs 42.9 mo (HR 0.81, 95% CI 0.68-0.96) |
1Reported efficacy is based on the 2021 update.
Preceding treatment
- VMP consolidation x 4 versus High-dose melphalan & autologous hematopoietic stem cell transplant x 1 to 2
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Bortezomib (Velcade) 1.3 mg/m2 IV or SC once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
28-day cycle for 2 cycles
Subsequent treatment
- Lenalidomide maintenance
Regimen variant #3, 2 cycles post-transplant with higher-dose dex
Study | Dates of enrollment | Evidence |
---|---|---|
Roussel et al. 2014 (IFM 2008) | 2009 | Phase 2 |
Two months after hematologic recovery, patients without progressive disease began treatment.
Preceding treatment
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15
Supportive therapy
- Low–molecular weight heparin (LMWH) for DVT prophylaxis
- Antiviral therapy with example valacyclovir given, for herpes zoster prevention
- Antibiotic prophylaxis with example amoxicillin given, for bacterial infections
21-day cycle for 2 cycles
Subsequent treatment
- Lenalidomide maintenance
Regimen variant #4, 5 cycles, no transplant
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Attal et al. 2017 (IFM 2009) | 2010-2012 | Phase 3 (E-de-esc) | Melphalan, then auto HSCT | Inferior PFS (primary endpoint) |
Richardson et al. 2022 (DETERMINATION) | 2010-10-01 to 2018-01-30 | Phase 3 (E-de-esc) | Melphalan, then auto HSCT | Inferior PFS (primary endpoint) |
Preceding treatment
- RVD induction x 3
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Dexamethasone (Decadron) 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycle for 5 cycles
Subsequent treatment
- Lenalidomide maintenance
Regimen variant #4, 5 cycles, no transplant, SC bortezomib
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Richardson et al. 2022 (DETERMINATION) | 2010-10-01 to 2018-01-30 | Phase 3 (E-de-esc) | Melphalan, then auto HSCT | Inferior PFS (primary endpoint) |
Preceding treatment
- RVD induction x 3
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 SC once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Dexamethasone (Decadron) 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycle for 5 cycles
Subsequent treatment
- Lenalidomide maintenance
Regimen variant #6, 8 cycles, no transplant
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jacobus et al. 2016 (ECOG E1A05) | 2008-2010 | Phase 3 (E-esc) | Rd | Not reported |
Note: this trial closed early due to poor accrual so only descriptive results are available.
Preceding treatment
- Dexamethasone-based induction x 1 to 6 cycles
Targeted therapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15
21-day cycle for 8 cycles
References
- Retrospective: Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. link to original article PubMed
- IFM 2008: Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01206205
- ECOG E1A05: Jacobus SJ, Rajkumar SV, Weiss M, Stewart AK, Stadtmauer EA, Callander NS, Dreosti LM, Lacy MQ, Fonseca R. Randomized phase III trial of consolidation therapy with bortezomib-lenalidomide-Dexamethasone (VRd) vs bortezomib-dexamethasone (Vd) for patients with multiple myeloma who have completed a dexamethasone based induction regimen. Blood Cancer J. 2016 Jul 29;6(7):e448. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00522392
- IFM 2009: Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01191060
- EMN02/HOVON-95: Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. link to original article PubMed NCT01208766
- Update: Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- DETERMINATION: Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. Epub 2022 Jun 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01208662
Tandem melphalan, then auto HSCT
Protocol variant #1, MEL100 x 2
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Palumbo et al. 2010 | 2005-2007 | Phase 2 | VGPR or better: 82% |
Preceding treatment
- PAD doxil induction x 4
Chemotherapy
- Melphalan (Alkeran) 100 mg/m2 IV once (day not specified)
Supportive therapy
- Autologous stem cells re-infused on unspecified day
Two courses
Subsequent treatment
- RP maintenance
Protocol variant #2, MEL140, then MEL200
Study | Dates of enrollment | Evidence |
---|---|---|
Attal et al. 2006 (IFM 99-02) | 2000-2003 | Non-randomized part of phase 3 RCT |
Preceding treatment
- VAD induction x 3 to 4
Chemotherapy
- Melphalan (Alkeran) as follows:
- First transplant: 140 mg/m2 IV once (day not specified)
- Second transplant: 200 mg/m2 IV once (day not specified)
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
Subsequent treatment
- Observation versus thalidomide maintenance
Protocol variant #3, MEL200 x 2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mai et al. 2016 (GMMG-HD2) | 1998-2002 | Phase 3 (E-esc) | Melphalan, then auto HSCT | Non-inferior EFS24 (primary endpoint) |
Lokhorst et al. 2009 (HOVON-50) | 2001-2005 | Non-randomized part of phase 3 RCT | ||
Palumbo et al. 2009 (GIS MM2001) | 2001-2006 | Phase 3 (C) | MEL100, then auto HSCT x 2 | Superior PFS |
Krishnan et al. 2011 (BMT CTN 0102) | 2003-2007 | Phase 3 (C) | MEL200, then auto HSCT, then RIC allo HSCT | Did not meet primary endpoint of PFS36 |
Sonneveld et al. 2012 (GMMG-HD4) | 2005-2008 | Non-randomized part of phase 3 RCT | ||
Palumbo et al. 2014 (MPRvsMEL200) | 2007-2009 | Phase 3 (E-esc) | MPR consolidation | Superior PFS (primary endpoint) Median PFS: 43 vs 22.4 mo (HR 0.44, 95% CI 0.32-0.61) Superior OS (secondary endpoint) OS48: 81.6% vs 65.3% (HR 0.55, 95% CI 0.32-0.93) |
Gay et al. 2015 (EMN-441) | 2009-2011 | Phase 3 (C) | CRd consolidation | Superior PFS (primary endpoint) Median PFS: 43.3 vs 28.6 mo (HR 0.40, 95% CI 0.25-0.625) |
Preceding treatment
Chemotherapy
- Melphalan (Alkeran) 200 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
Two courses
Subsequent treatment
- HOVON-50, if induced with VAD: Interferon alfa maintenance
- HOVON-50, if induced with TAD: Thalidomide maintenance
- BMT CTN 0102: No further treatment versus Thal-Dex maintenance x 1 y
- GMMG-HD4, if induced with PAD: Bortezomib maintenance x 2 y
- GMMG-HD4, if induced with VAD: Thalidomide maintenance x 2 y
- MPRvsMEL200: Lenalidomide maintenance versus no further treatment
- EMN-441: Lenalidomide versus RP maintenance
Protocol variant #4, MEL200 x 2 (split doses)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Barlogie et al. 1997 (Total Therapy 1) | 1990-1994 | Non-randomized | CR rate: 40% | |
Bruno et al. 2007 | 1998-2004 | Pseudo-Mendelian randomization1 | MEL-auto HSCT x 1, then TBI, then allo HSCT | Inferior OS |
1Randomization was based on the availability of an HLA-identical sibling.
Note: reported efficacy for Total Therapy 1 is based on the 1999 update. Bruno et al. 2007 does not contain treatment details.
Preceding treatment
- Induction EDAP x 1
Chemotherapy
- Melphalan (Alkeran) 100 mg/m2 IV once per day on days -3 & -2
Supportive therapy
- Autologous stem cells re-infused on day 0
Two courses
Subsequent treatment
- Interferon alfa maintenance
References
- Total Therapy 1: Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997 Feb 1;89(3):789-93. link to original article PubMed
- Update: Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999 Jan 1;93(1):55-65. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pooled update: Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. link to original article link to PMC article PubMed
- IFM 99-02: Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T; IFM. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15;108(10):3289-94. Epub 2006 Jul 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00222053
- Pooled update: Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. link to original article link to PMC article PubMed
- Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedè P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007 Mar 15;356(11):1110-20. link to original article does not contain dosing details PubMed NCT00415987
- HOVON-50: Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00028886
- Update: van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. link to original article PubMed
- GIS MM2001: Palumbo A, Bringhen S, Bruno B, Falcone AP, Liberati AM, Grasso M, Ria R, Pisani F, Cangialosi C, Caravita T, Levi A, Meloni G, Nozza A, Pregno P, Gabbas A, Callea V, Rizzo M, Annino L, De Stefano V, Musto P, Baldi I, Cavallo F, Petrucci MT, Massaia M, Boccadoro M. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010 Mar 11;115(10):1873-9. Epub 2009 Dec 1. Erratum in: Blood. 2010 Sep 23;116(12):2195. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00950768
- Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2005-004714-32
- Update: Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. link to original article dosing details in abstract have been reviewed by our editors PubMed
- GIMEMA MM-BO2005: Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. link to original article PubMed NCT01134484
- Update: Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- BMT CTN 0102: Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; BMT CTN. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. Epub 2011 Sep 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00075829
- GMMG-HD4: Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN64455289
- Subgroup analysis: Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. link to original article PubMed
- Update: Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. link to original article PubMed
- Meta-analysis: Armeson KE, Hill EG, Costa LJ. Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment. Bone Marrow Transplant. 2013 Apr;48(4):562-7. Epub 2012 Sep 10. Review. link to original article link to PMC article PubMed
- MPRvsMEL200: Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00551928
- EMN-441: Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01091831
- GMMG-HD2: Mai EK, Benner A, Bertsch U, Brossart P, Hänel A, Kunzmann V, Naumann R, Neben K, Egerer G, Ho AD, Hillengass J, Raab MS, Neubauer A, Peyn A, Ko YD, Peter N, Scheid C, Goldschmidt H. Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial. Br J Haematol. 2016 Jun;173(5):731-41. Epub 2016 Mar 17. link to original article PubMed DRKS00008864
- EMN02/HOVON-95: Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. link to original article PubMed NCT01208766
- Update: Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. link to original article PubMed
- DSMM V: NCT00546988
Thalidomide & Dexamethasone (TD)
TD: Thalidomide & Dexamethasone
Thal-Dex: Thalidomide & Dexamethasone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cavo et al. 2010 (GIMEMA MM-BO2005) | 2006-2008 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Tandem MEL200 with auto HSCT consolidation, with interim Thal-Dex maintenance (see paper for details)
Targeted therapy
- Thalidomide (Thalomid) 100 mg PO once per day
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 20 to 23
Supportive therapy
- Acyclovir (Zovirax) prophylaxis recommended
35-day cycle for 2 cycles
Subsequent treatment
- Dexamethasone maintenance
References
- GIMEMA MM-BO2005: Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. link to original article PubMed NCT01134484
- Update: Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Thalidomide & Prednisolone (TP)
TP: Thalidomide & Prednisolone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Horvath et al. 2019 (VCAT) | 2012-2016 | Phase 3 (C) | VTP | Did not meet primary endpoint of CR + VGPR rate |
Preceding treatment
- Induction VDC x 3, then high-dose auto HSCT consolidation
Targeted therapy
- Thalidomide (Thalomid) as follows:
- Cycles 1 to 13: 100 mg PO once per day on days 1 to 28
Glucocorticoid therapy
- Prednisolone (Millipred) 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
28-day cycles
References
- VCAT: Horvath N, Spencer A, Kenealy M, Joshua D, Campbell PJ, Lee JJ, Hou J, Qiu L, Kalff A, Khong T, Londhe A, Siggins S, van Kooten Losio M, Eisbacher M, Prince HM. Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study. Leuk Lymphoma. 2019 Sep;60(9):2122-2133. Epub 2019 Feb 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01539083
VMP
VMP: Velcade (Bortezomib), Melphalan, Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Mateos et al. 2006 | 2004-2005 | Phase 1/2 |
Note: this was the phase II portion of this phase I/II study.
Preceding treatment
- VMP induction
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
Chemotherapy
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
35-day cycle for 5 cycles
References
- Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, Díaz-Mediavilla J, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, de Arriba F, Alegre A, Oriol A, Carrera D, García-Laraña J, García-Sanz R, Bladé J, Prósper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006 Oct 1;108(7):2165-72. Epub 2006 Jun 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EMN02/HOVON-95: Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30. Erratum in: Lancet Haematol. 2020 Jun;7(6):e443. Erratum in: Lancet Haematol. 2020 Nov;7(11):e785. link to original article PubMed NCT01208766
- Update: Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M. Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14. link to original article PubMed
VTD
VTD: Velcade (Bortezomib), Thalidomide, Dexamethasone
Regimen variant #1, "vTD"
Study | Dates of enrollment | Evidence |
---|---|---|
Lok et al. 2014 | 2011-2013 | Non-randomized |
Preceding treatment
Targeted therapy
- Bortezomib (Velcade) 1 mg/m2 SC once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg (route not specified) once per day on days 1 to 4
21-day cycle for 2 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Cavo et al. 2010 (GIMEMA MM-BO2005) | 2006-2008 | Non-randomized part of phase 3 RCT |
VTD consolidation is to begin 3 months after the second transplant.
Preceding treatment
- VTD induction, then high-dose melphalan with tandem autologous hematopoietic stem cell transplant consolidation
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 35
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
Supportive therapy
- Acyclovir (Zovirax) prophylaxis recommended
35-day cycle for 2 cycles
Subsequent treatment
- Dexamethasone maintenance
Regimen variant #3
Study | Dates of enrollment | Evidence |
---|---|---|
Ladetto et al. 2010 (GIMEMA VEL-03-096) | 2004-08 to 2007-07 | Phase 2 |
Preceding treatment
- Melphalan, then HSCT consolidation, with at least a very good partial response (VGPR)
Targeted therapy
- Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15, 22
- Thalidomide (Thalomid) 50 mg PO once per day, increased by 50 mg each week, up to a maximum of 200 mg PO once per day
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18
35-day cycle for 4 cycles
References
- GIMEMA VEL-03-096: Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, Crippa C, De Rosa L, Pregno P, Grasso M, Liberati AM, Caravita T, Pisani F, Guglielmelli T, Callea V, Musto P, Cangialosi C, Passera R, Boccadoro M, Palumbo A. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010 Apr 20;28(12):2077-84. Epub 2010 Mar 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2004-000531-28
- Update: Ferrero S, Ladetto M, Drandi D, Cavallo F, Genuardi E, Urbano M, Caltagirone S, Grasso M, Rossini F, Guglielmelli T, Cangialosi C, Liberati AM, Callea V, Caravita T, Crippa C, De Rosa L, Pisani F, Falcone AP, Pregno P, Oliva S, Terragna C, Musto P, Passera R, Boccadoro M, Palumbo A. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival. Leukemia. 2015 Mar;29(3):689-95. Epub 2014 Jul 16. link to original article PubMed
- GIMEMA MM-BO2005: Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01134484
- Update: Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous bortezomib incorporated into the bortezomib-thalidomide-dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Maintenance after first-line therapy
Note that there is no crisp distinction between consolidation and maintenance. Generally regimens that are intended for a long or indefinite duration would be considered maintenance, whereas regimens with a short intended course would be considered consolidation.
Bortezomib monotherapy
Regimen variant #1, IV x 2 years
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sonneveld et al. 2012 (HOVON-65) | 2005-2008 | Phase 3 (E-switch-ooc) | Thalidomide | Superior PFS1 (primary endpoint) |
Sonneveld et al. 2012 (GMMG-HD4) | 2005-2008 | Phase 3 (E-switch-ooc) | Thalidomide | Superior PFS1 (primary endpoint) |
1In the initial publication, this arm seemed to have an overall survival advantage; this was no longer present in the updated report of 2017. HOVON-65/GMMG-HD4 was a single phase 3 RCT but the consolidation was different by group, so is reported here as 2 distinct trials.
Preceding treatment
- HOVON-65: High-dose melphalan with single autologous hematopoietic stem cell transplant consolidation
- GMMG-HD4: High-dose melphalan with tandem autologous hematopoietic stem cell transplants consolidation
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once on day 1
14-day cycle for 52 cycles (2 years)
Regimen variant #2, SC, indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Larocca et al. 2016 (MMY2069) | 2010-10 to 2012-08 | Phase 2 |
Preceding treatment
- Induction VP x 9
References
- HOVON-65: Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN64455289
- Subgroup analysis: Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. link to original article PubMed
- Update: Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. link to original article PubMed
- GMMG-HD4: Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN64455289
- Subgroup analysis: Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. link to original article PubMed
- Update: Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. link to original article PubMed
- MMY2069: Larocca A, Bringhen S, Petrucci MT, Oliva S, Falcone AP, Caravita T, Villani O, Benevolo G, Liberati AM, Morabito F, Montefusco V, Passera R, De Rosa L, Omedé P, Vincelli ID, Spada S, Carella AM, Ponticelli E, Derudas D, Genuardi M, Guglielmelli T, Nozzoli C, Aghemo E, De Paoli L, Conticello C, Musolino C, Offidani M, Boccadoro M, Sonneveld P, Palumbo A. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. Leukemia. 2016 Jun;30(6):1320-6. Epub 2016 Feb 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01190787
Bortezomib & Dexamethasone (Vd)
VD: Velcade (Bortezomib) & low-dose dexamethasone
Regimen
Study | Evidence | Efficacy |
---|---|---|
Berdeja et al. 2017 (SCRI MM 23) | Phase 2 | ORR: 91% |
Note: this is the modified treatment schema.
Preceding treatment
- Induction BBD x 8
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV or SC once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once on day 1
14-day cycle for 52 cycles (2 years)
References
- SCRI MM 23: Berdeja JG, Bauer T, Arrowsmith E, Essell J, Murphy P, Reeves JA Jr, Boccia RV, Donnellan W, Flinn I. Phase II study of bendamustine, bortezomib and dexamethasone (BBD) in the first-line treatment of patients with multiple myeloma who are not candidates for high dose chemotherapy. Br J Haematol. 2017 Apr;177(2):254-262. Epub 2017 Feb 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01056276
Carfilzomib monotherapy
Regimen variant #1, bi-weekly
Study | Dates of enrollment | Evidence |
---|---|---|
Bringhen et al. 2014 (IST-CAR-506) | 2011-06-21 to 2012-09-15 | Phase 2 |
Preceding treatment
- Induction CCyd x 9
Regimen variant #2, weekly
Study | Dates of enrollment | Evidence |
---|---|---|
Bringhen et al. 2017 (IST-CAR-561) | 2013-04-10 to 2015-08-24 | Phase 1/2 |
Note: this was the MTD established for the phase 2 portion of the trial.
Preceding treatment
- Induction wKCyd x 9
References
- IST-CAR-506: Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omedé P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. Epub 2014 May 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01346787
- IST-CAR-561: Bringhen S, D'Agostino M, De Paoli L, Montefusco V, Liberati AM, Galieni P, Grammatico S, Muccio VE, Esma F, De Angelis C, Musto P, Ballanti S, Offidani M, Petrucci MT, Gaidano G, Corradini P, Palumbo A, Sonneveld P, Boccadoro M. Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. Leukemia. 2018 Apr;32(4):979-985. Epub 2017 Nov 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01857115
Carfilzomib & Lenalidomide (KR)
KR: Kyprolis (Carfilzomib) & Revlimid (Lenalidomide)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gay et al. 2021 (FORTE) | 2015-2017 | Randomized Phase 2 (E-esc) | Lenalidomide | Superior PFS (co-primary endpoint) PFS36: 75% vs 65% (HR 0.64, 95% CI 0.44-0.94) |
Note: treatment details are as provided in a 2020 ASH abstract.
Targeted therapy
- Carfilzomib (Kyprolis) as follows:
- Cycles 1 up to 26: 70 mg/m2 IV once per day on days 1 & 15
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycles
References
- FORTE: Gay F, Musto P, Rota-Scalabrini D, Bertamini L, Belotti A, Galli M, Offidani M, Zamagni E, Ledda A, Grasso M, Ballanti S, Spadano A, Cea M, Patriarca F, D'Agostino M, Capra A, Giuliani N, de Fabritiis P, Aquino S, Palmas A, Gamberi B, Zambello R, Petrucci MT, Corradini P, Cavo M, Boccadoro M. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. Lancet Oncol. 2021 Dec;22(12):1705-1720. Epub 2021 Nov 11. link to original article PubMed NCT02203643
Daratumumab monotherapy
Regimen variant #1, q4wk indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Mateos et al. 2017 (ALCYONE) | 2015-02-09 to 2016-07-14 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Induction Dara-VMP x 9
Targeted therapy
- Daratumumab (Darzalex) 16 mg/kg IV once on day 1
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV or PO once on day 1, prior to daratumumab
28-day cycles
Regimen variant #2, q8wk x 2y
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moreau et al. 2019 (CASSIOPEIA part 2) | 2016-2018 | Phase 3 (E-esc) | Observation | Superior PFS (co-primary endpoint) Median PFS: NYR vs 46.7 mo (HR 0.53, 95% CI 0.42-0.68) |
Note: the protocol is somewhat confusing about what dose of steroids to use as premedication. See the original paper.
Targeted therapy
- Daratumumab (Darzalex) 16 mg/kg IV once on day 1
56-day cycle for 13 cycles (2 years)
References
- ALCYONE: Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. Epub 2017 Dec 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02195479
- CASSIOPEIA part 2: Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, Béné MC, Zweegman S, Caillon H, Caillot D, Corre J, Delforge M, Dejoie T, Doyen C, Facon T, Sonntag C, Fontan J, Mohty M, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Macro M, Orsini-Piocelle F, Roussel M, Stoppa AM, van de Donk NWCJ, Wuillème S, Broijl A, Touzeau C, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Offner F, Escoffre-Barbe M, Eveillard JR, Garidi R, Ahmadi T, Krevvata M, Zhang K, de Boer C, Vara S, Kampfenkel T, Vanquickelberghe V, Vermeulen J, Avet-Loiseau H, Sonneveld P. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1378-1390. Epub 2021 Sep 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02541383
Ixazomib monotherapy
Regimen variant #1, indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Kumar et al. 2014 (C16005) | 2010-2012 | Phase 1/2 |
Preceding treatment
- Induction IRd x 12
Regimen variant #2, 2-year course
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dimopoulos et al. 2018 (TOURMALINE-MM3) | 2014-2016 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 26.5 vs 21.3 mo (HR 0.72, 95% CI 0.58-0.89) |
Dimopoulos et al. 2020 (TOURMALINE-MM4) | 2015-2018 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 17.4 vs 9.4 mo (HR 0.66, 95% CI 0.54-0.80) |
Note: dose was escalated in cycle 5 if the prior dose was tolerated.
Preceding treatment
- TOURMALINE-MM3: Melphalan with auto HSCT consolidation
- TOURMALINE-MM4: Standard-of-care induction therapy x 6 to 12 months
Targeted therapy
- Ixazomib (Ninlaro) as follows:
- Cycles 1 to 4: 3 mg PO once per day on days 1, 8, 15
- Cycles 5 to 26: 4 mg PO once per day on days 1, 8, 15
28-day cycle for up to 26 cycles (2 years)
References
- C16005: Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Di Bacco A, Estevam J, Gupta N, Hui AM, Rajkumar V, Richardson PG. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol. 2014 Dec;15(13):1503-12. Epub 2014 Nov 14. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01217957
- Update: Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Rajkumar SV, Richardson PG. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance. Leukemia. 2019 Jul;33(7):1736-1746. Epub 2019 Jan 29. link to original article link to PMC article PubMed
- TOURMALINE-MM3: Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, Goldschmidt H, Maisnar V, Moreau P, Min CK, Pluta A, Chng WJ, Kaiser M, Zweegman S, Mateos MV, Spencer A, Iida S, Morgan G, Suryanarayan K, Teng Z, Skacel T, Palumbo A, Dash AB, Gupta N, Labotka R, Rajkumar SV; TOURMALINE-MM3 study group. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Jan 19;393(10168):253-264. Epub 2018 Dec 10. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02181413
- TOURMALINE-MM4: Dimopoulos MA, Špička I, Quach H, Oriol A, Hájek R, Garg M, Beksac M, Bringhen S, Katodritou E, Chng WJ, Leleu X, Iida S, Mateos MV, Morgan G, Vorog A, Labotka R, Wang B, Palumbo A, Lonial S; TOURMALINE-MM4 study group. Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol. 2020 Dec 1;38(34):4030-4041. Epub 2020 Oct 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02312258
Isa-Rd
Isa-Rd: Isatuximab, Revlimid (Lenalidomide), low-dose dexamethasone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Facon et al. 2024 (IMROZ) | 2017-12 to 2019-03 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Induction Isa-RVd x 4
Targeted therapy
- Isatuximab (Sarclisa) as follows:
- Cycles 1 to 17: 10 mg/kg IV once per day on days 1 & 15
- Cycle 18 onwards: 10 mg/kg IV once on day 1
- Lenalidomide (Revlimid) by the following laboratory-based criteria:
- eGFR 60 mL/min/1.73m2 or more: 25 mg PO once per day on days 1 to 21
- eGFR 30 up to 60 mL/min/1.73m2: 10 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22
28-day cycles
References
- IMROZ: Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hájek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Brégeault MF, Macé S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Jun 3. Epub ahead of print. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03319667
KRd
KRd: Kyprolis (Carfilzomib), Revlimid (Lenalidomide), low-dose dexamethasone
CRd: Carfilzomib, Revlimid (Lenalidomide), low-dose dexamethasone
Regimen variant #1, biweekly carfilzomib
Study | Dates of enrollment | Evidence |
---|---|---|
Jakubowiak et al. 2012 (UMCC 2009.056) | 2009-2011 | Phase 1/2 |
This is the MTD dosing in this phase 1/2 trial.
Preceding treatment
- Induction KRd x 8
Targeted therapy
- Carfilzomib (Kyprolis) 36 mg/m2 IV once per day on days 1, 2, 15, 16
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg (route not specified) once per day on days 1, 8, 15, 22
28-day cycle for 16 cycles
Subsequent treatment
- UMCC 2009.056: It was recommended that patients proceed to lenalidomide maintenance
Regimen variant #2, carfilzomib 3 weeks on/1 week off
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dytfeld et al. 2023 (ATLAS-MM) | 2016-2020 | Phase 3 (E-esc) | Lenalidomide | Superior PFS (primary endpoint) Median PFS: 59.1 vs 41.4 mo (HR 0.51, 95% CI 0.31-0.86) |
Note: This trial is labeled ATLAS-MM here, to distinguish from trials named ATLAS in multiple other cancer subtypes.
Preceding treatment
Targeted therapy
- Carfilzomib (Kyprolis) 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22
28-day cycle for 36 cycles
Subsequent treatment
- Lenalidomide maintenance
References
- UMCC 2009.056: Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. Epub 2012 Jun 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01029054
- ATLAS-MM: Dytfeld D, Wróbel T, Jamroziak K, Kubicki T, Robak P, Walter-Croneck A, Czyż J, Tyczyńska A, Druzd-Sitek A, Giannopoulos K, Nowicki A, Szczepaniak T, Łojko-Dankowska A, Matuszak M, Gil L, Puła B, Rybka J, Majcherek M, Usnarska-Zubkiewicz L, Szukalski Ł, Końska A, Zaucha JM, Walewski J, Mikulski D, Czabak O, Robak T, Lahoud OB, Zonder JA, Griffith K, Stefka A, Major A, Derman BA, Jakubowiak AJ. Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Feb;24(2):139-150. Epub 2023 Jan 12. link to original articledosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02659293
- HRQoL analysis: Kubicki T, Jamroziak K, Robak P, Czyż J, Tyczyńska A, Druzd-Sitek A, Giannopoulos K, Wróbel T, Nowicki A, Szczepaniak T, Łojko-Dankowska A, Matuszak M, Gil L, Puła B, Szukalski Ł, Końska A, Zaucha JM, Walewski J, Mikulski D, Czabak O, Robak T, Kruk-Kwapisz D, Derman BA, Major A, Jakubowiak AJ, Dytfeld D. Health-related quality of life in patients with multiple myeloma treated in the phase 3 ATLAS trial of post-transplant maintenance with carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone. Pol Arch Intern Med. 2024 May 28;134(5):16749. Epub 2024 May 14. link to original article PubMed
Lenalidomide monotherapy
Regimen variant #1, indefinite 10 mg 21/28
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Palumbo et al. 2007a | 2005 | Phase 2 | ||
Palumbo et al. 2010 | 2005-2007 | Phase 2 | ||
Palumbo et al. 2012 (MM-015) | 2007-02 to 2008-09 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) |
Palumbo et al. 2014 (MPRvsMEL200) | 2007-2009 | Phase 3 (E-esc) | Observation | Superior PFS (primary endpoint) Median PFS: 41.9 vs 21.6 mo (HR 0.47, 95% CI 0.33-0.65) |
Stewart et al. 2015 (ECOG E1A06) | 2008-2011 | Non-randomized part of phase 3 RCT | ||
Gay et al. 2015 (EMN-441) | 2009-2011 | Phase 3 (C) | RP | Did not meet primary endpoint of PFS |
Magarotto et al. 2016 (EMN01) | 2009-2012 | Phase 3 (C) | RP | Not reported |
Zweegman et al. 2016 (HOVON87/NMSG18) | 2009-2012 | Phase 3 (E-switch-ic) | Thalidomide | Did not meet primary endpoint of PFS |
Jackson et al. 2018 (UK NCRI Myeloma XI) | 2011-01-13 to 2017-08-11 | Phase 3 (E-esc) | 1. Observation | Superior PFS (co-primary endpoint) Median PFS: 39 vs 20 mo (HR 0.46, 95% CI 0.41-0.53) |
2. Lenalidomide & Vorinostat | Did not meet co-primary endpoint of PFS | |||
Larocca et al. 2021 (RV-MM-PI-0752) | 2014-2017 | Phase 3 (E-de-esc) | Rd; continuous | Seems to have superior EFS (primary endpoint) Median EFS: 10.4 vs 6.9 mo (HR 0.70, 95% CI 0.51-0.95) |
Preceding treatment
- Palumbo et al. 2007a & MM-015: MPR induction x 9
- Palumbo et al. 2010: RP consolidation
- MPRvsMEL200: Tandem high-dose melphalan with autologous hematopoietic stem cell transplants versus MPR consolidation
- ECOG E1A06: mPR induction x 12
- EMN-441: Tandem high-dose melphalan with autologous hematopoietic cell transplants versus CRd consolidation
- EMN01: CPR versus MPR versus Rd induction x 9
- HOVON87/NMSG18: MPR induction x 9
- RV-MM-PI-0752: Rd induction x 9
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Supportive therapy
- Varies depending on reference:
- MM-015: Aspirin 75 to 100 mg PO once per day
- Palumbo et al. 2007a and Palumbo et al. 2010: Aspirin 100 mg PO once per day
- ECOG E1A06: Aspirin was required (dose not specified)
- Full anticoagulation was used for patients at "higher risk" for DVT
- EMN01: Aspirin or LMWH or Warfarin (Coumadin) at physician's discretion (mandatory)
- ECOG E1A06: Pamidronate (Aredia) 90 mg IV once per month recommended for patients with "active bone disease"
- Palumbo et al. 2007a: Ciprofloxacin (Cipro) 500 mg PO twice per day
28-day cycles
Protocol variant #2, indefinite 10 -> 15 mg per day with higher dose lead-in
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Attal et al. 2012 (IFM 2005-02) | 2006-2008 | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 41 vs 23 mo (HR 0.50) |
Note: this is "Maintenance Study 2" listed in the package insert.
Targeted therapy
- Lenalidomide (Revlimid) as follows:
- Cycles 1 & 2: 25 mg PO once per day on days 1 to 21
- Cycle 3: 10 mg PO once per day on days 1 to 90
- Cycle 4 onwards: 15 mg PO once per day on days 1 to 90
Supportive therapy
- "Thromboprophylaxis was not used"
28-day cycle for 2 cycles, then 90-day cycles
Regimen variant #3, indefinite 10 -> 15 mg per day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McCarthy et al. 2012 (CALGB 100104) | 2005-2009 | Phase 3 (E-RT-esc) | Placebo | Superior OS1 (secondary endpoint) Median OS: 113.8 vs 84.1 mo (HR 0.61, 95% CI 0.46-0.81) Superior TTP (primary endpoint) |
1Reported efficacy is based on the 2017 update.
Note: this is "Maintenance Study 1" listed in the package insert. There may be some dosing discrepancies between papers; this dose is the one described in the 2017 update.
Preceding treatment
- Melphalan with auto HSCT consolidation, within 100 to 120 days
Targeted therapy
- Lenalidomide (Revlimid) as follows:
- Cycle 1: 10 mg PO once per day on days 1 to 90
- Cycle 2 onwards: 15 mg PO once per day on days 1 to 90
Supportive therapy
- Patients at high risk of deep venous thrombosis (DVT) or pulmonary embolism (PE) received Aspirin, low molecular weight heparin, or Warfarin (Coumadin) unless contraindicated. High risk patients were defined as people with: history of diabetes, coronary artery disease, "DVT/PE, significant family history, performance status of at least 2, smoking history, use of oral contraceptives, and[/or] concurrent use of epoetin."
90-day cycles
Regimen variant #4, 2 years of 25 mg 21/28
Study | Dates of enrollment | Evidence |
---|---|---|
Korde et al. 2016 (NCI 12-C-0107) | 2011-2013 | Phase 2 |
Korde et al. 2016 (NCI 11-C-0221) | 2011-2013 | Phase 2 |
Preceding treatment
- Induction KRd x 8
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycle for up to 24 cycles
Regimen variant #5, 1 year of 10 to 15 mg per day
Study | Dates of enrollment | Evidence |
---|---|---|
Roussel et al. 2014 (IFM 2008) | 2009 | Phase 2 |
Attal et al. 2017 (IFM 2009) | 2010-2012 | Non-randomized part of phase 3 RCT |
Note: Thalidomide dose was increased only if the starting dose was tolerated.
Preceding treatment
- RVD consolidation
Targeted therapy
- Lenalidomide (Revlimid) as follows:
- Months 1 to 3: 10 mg PO once per day
- Months 4 to 12: 15 mg PO once per day
12-month course
Regimen variant #6, indefinite 25 mg 21/28
Study | Dates of enrollment | Evidence |
---|---|---|
Jakubowiak et al. 2012 (UMCC 2009.056) | 2009-2011 | Phase 1/2 |
Preceding treatment
- Induction KRd x 24
References
- Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foà R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. Epub 2007 Sep 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2005-004714-32
- Update: Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. link to original article dosing details in abstract have been reviewed by our editors PubMed
- CALGB 100104: McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00114101
- Update: Holstein SA, Jung SH, Richardson PG, Hofmeister CC, Hurd DD, Hassoun H, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, van Besien K, Gentile TG, Isola L, Maziarz RT, Bashey A, Landau H, Martin T, Qazilbash MH, Rodriguez C, McClune B, Schlossman RL, Smith SE, Hars V, Owzar K, Jiang C, Boyd M, Schultz C, Wilson M, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Linker C, Anderson KC, McCarthy PL. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial. Lancet Haematol. 2017 Sep;4(9):e431-e442. Epub 2017 Aug 17. link to original article link to PMC article PubMed
- IFM2005-02: Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1782-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00430365
- Update: Abstract: Michel Attal, MD, Valerie Cances Lauwers, Gerald Marit, Denis Caillot, Thierry Facon, MD, Cyrille Hulin, Philippe Moreau, MD, Claire Mathiot, Murielle Roussel, Catherine Payen, H. Avet-Loiseau and Jean Luc Harousseau. Maintenance Treatment with Lenalidomide After Transplantation for MYELOMA : Final Analysis of the IFM 2005-02. ASH 2010 Abstract 310.
- UMCC 2009.056: Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. Epub 2012 Jun 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01029054
- MM-015: Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. Erratum in: N Engl J Med. 2012 Jul 19;367(3):285. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00405756
- IFM 2008: Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01206205
- MPRvsMEL200: Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00551928
- GMMG-MM5: Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, Munder M, Jauch A, Schurich B, Hielscher T, Merz M, Huegle-Doerr B, Seckinger A, Hose D, Hillengass J, Raab MS, Neben K, Lindemann HW, Zeis M, Gerecke C, Schmidt-Wolf IG, Weisel K, Scheid C, Salwender H, Goldschmidt H. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015 Aug;29(8):1721-9. Epub 2015 Mar 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2010-019173-16
- Subgroup analysis: Merz M, Salwender H, Haenel M, Mai EK, Bertsch U, Kunz C, Hielscher T, Blau IW, Scheid C, Hose D, Seckinger A, Jauch A, Hillengass J, Raab MS, Schurich B, Munder M, Schmidt-Wolf IG, Gerecke C, Lindemann HW, Zeis M, Weisel K, Duerig J, Goldschmidt H. Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial. Haematologica. 2015 Jul;100(7):964-9. Epub 2015 Apr 3. link to original article link to PMC article PubMed
- Update: Goldschmidt H, Mai EK, Dürig J, Scheid C, Weisel KC, Kunz C, Bertsch U, Hielscher T, Merz M, Munder M, Lindemann HW, Hügle-Dörr B, Tichy D, Giesen N, Hose D, Seckinger A, Huhn S, Luntz S, Jauch A, Elmaagacli A, Rabold B, Fuhrmann S, Brossart P, Goerner M, Bernhard H, Hoffmann M, Hillengass J, Raab MS, Blau IW, Hänel M, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG). Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. Leukemia. 2020 Jul;34(7):1853-1865. Epub 2020 Feb 7. link to original article PubMed
- ECOG E1A06: Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, Rajkumar SV. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015 Sep 10;126(11):1294-301. Epub 2015 Jul 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00602641
- EMN-441: Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01091831
- EMN01: Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. Epub 2016 Jan 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01093196
- HOVON87/NMSG18: Zweegman S, van der Holt B, Mellqvist UH, Salomo M, Bos GM, Levin MD, Visser-Wisselaar H, Hansson M, van der Velden AW, Deenik W, Gruber A, Coenen JL, Plesner T, Klein SK, Tanis BC, Szatkowski DL, Brouwer RE, Westerman M, Leys MR, Sinnige HA, Haukås E, van der Hem KG, Durian MF, Mattijssen EV, van de Donk NW, Stevens-Kroef MJ, Sonneveld P, Waage A. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 Mar 3;127(9):1109-16. Epub 2016 Jan 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2007-004007-34
- Abstract: Meta-analysis: Michel Attal, Antonio Palumbo, Sarah A. Holstein, Valerie Lauwers-Cances, Maria Teresa Petrucci, Paul G. Richardson, Cyrille Hulin, Patrizia Tosi, Kenneth Carl Anderson, Denis Caillot, Valeria Magarotto, Philippe Moreau, Gerald Marit, Zhinuan Yu, Philip L. McCarthy. Lenalidomide (LEN) maintenance (MNTC) after high-dose melphalan and autologous stem cell transplant (ASCT) in multiple myeloma (MM): A meta-analysis (MA) of overall survival (OS). J Clin Oncol 34, 2016 (suppl; abstr 8001) link to abstract
- NCI 11-C-0221: Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With carfilzomib-lenalidomide-dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01402284
- NCI 12-C-0107: Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With carfilzomib-lenalidomide-dexamethasone with lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01572480
- IFM 2009: Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01191060
- UK NCRI Myeloma XI: Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Hockaday A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ; UK NCRI Haemato-oncology Clinical Studies Group. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019 Jan;20(1):57-73. Epub 2018 Dec 14. link to original article link to PMC article PubMed NCT01554852
- Update: Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Waterhouse A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Allotey D, Shafeek S, Jenner MW, Cook G, Russell NH, Kaiser MF, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Clinical Studies Group UNHO. Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial. Haematologica. 2021 Jul 1;106(7):1957-1967. link to original article link to PMC article PubMed
- Update: Jenner MW, Pawlyn C, Davies FE, Menzies T, Hockaday A, Olivier C, Jones JR, Karunanithi K, Lindsay J, Kishore B, Cook G, Drayson MT, Kaiser MF, Owen RG, Gregory W, Cairns DA, Morgan GJ, Jackson GH; UK National Cancer Research Institute (NCRI) Haemato-oncology Clinical Studies Group. The addition of vorinostat to lenalidomide maintenance for patients with newly diagnosed multiple myeloma of all ages: results from 'Myeloma XI', a multicentre, open-label, randomised, phase III trial. Br J Haematol. 2023 Apr;201(2):267-279. Epub 2022 Dec 21. link to original article link to PMC article PubMed
- RV-MM-PI-0752: Larocca A, Bonello F, Gaidano G, D'Agostino M, Offidani M, Cascavilla N, Capra A, Benevolo G, Tosi P, Galli M, Marasca R, Giuliani N, Bernardini A, Antonioli E, Rota-Scalabrini D, Cellini C, Pompa A, Monaco F, Patriarca F, Caravita di Toritto T, Corradini P, Tacchetti P, Boccadoro M, Bringhen S. Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Blood. 2021 Jun 3;137(22):3027-3036. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02215980
- AURIGA: NCT03901963
- DRAMMATIC: NCT04071457
- LenaMain-Trial: NCT00891384
- MagnetisMM-7: NCT05317416
- MajesTEC-4: NCT05243797
Lenalidomide & Dexamethasone (Rd)
Rd: Revlimid (Lenalidomide) & low-dose dexamethasone
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mai et al. 2024 (GMMG-HD6) | 2015-06-29 to 2017-09-11 | Phase 3 (C) | Elo-Rd | Did not meet primary endpoint of PFS |
Targeted therapy
- Lenalidomide (Revlimid) as follows:
- Cycles 1 to 3: 10 mg PO once per day on days 1 to 28
- Cycles 4 to 26: 15 mg PO once per day on days 1 to 28
Glucocorticoid therapy
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 6: 12 mg PO once per day on days 1 & 15
- Cycles 7 to 26: 12 mg PO once on day 1
28-day cycle for 26 cycles
Regimen variant #2, 15/20
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rosiñol et al. 2023 (GEM2014MAIN) | 2014-11 to 2017-05 | Phase 3 (C) | IRd | Did not meet primary endpoint of PFS12 |
Preceding treatment
- VRd consolidation x 2
Targeted therapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 9 to 12
28-day cycle for 24 cycles
Subsequent treatment
- GEM2014MAIN, negative MRD at 2 years: No further treatment
- GEM2014MAIN, positive MRD at 2 years: Rd continuation x 36 cycles (60 cycles total)
Regimen variant #3, 25/40 indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Durie et al. 2016 (SWOG S0777) | 2008-2012 | Non-randomized part of phase 3 RCT |
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
28-day cycles
Regimen variant #4, indefinite with renal adjustment
Study | Dates of enrollment | Evidence |
---|---|---|
Facon et al. 2024 (IMROZ) | 2017-12 to 2019-03 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Induction RVd x 4
Targeted therapy
- Lenalidomide (Revlimid) by the following laboratory-based criteria:
- eGFR 60 mL/min/1.73m2 or more: 25 mg PO once per day on days 1 to 21
- eGFR 30 up to 60 mL/min/1.73m2: 10 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22
28-day cycles
References
- SWOG S0777: Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017 Feb 4;389(10068):519-527. Epub 2016 Dec 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00644228
- GEM2014MAIN: Rosiñol L, Oriol A, Ríos R, Blanchard MJ, Jarque I, Bargay J, Hernández MT, Cabañas V, Carrillo-Cruz E, Sureda A, Martínez-López J, Krsnik I, González ME, Casado LF, Martí JM, Encinas C, de Arriba F, Palomera L, Sampol A, González-Montes Y, Cabezudo E, Paiva B, Puig N, Cedena MT, de la Cruz J, Mateos MV, San Miguel J, Lahuerta JJ, Bladé J. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood. 2023 Nov 2;142(18):1518-1528. Epub 2023 Jul 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02406144
- GMMG-HD6: Mai EK, Goldschmid H, Miah K, Bertsch U, Besemer B, Hänel M, Krzykalla J, Fenk R, Schlenzka J, Munder M, Dürig J, Blau IW, Huhn S, Hose D, Jauch A, Kunz C, Mann C, Weinhold N, Scheid C, Schroers R, von Metzler I, Schieferdecker A, Thomalla J, Reimer P, Mahlberg R, Graeven U, Kremers S, Martens UM, Kunz C, Hensel M, Benner A, Seidel-Glätzer A, Weisel KC, Raab MS, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG) HD6 investigators. Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e101-e113. Erratum in: Lancet Haematol. 2024 Mar;11(3):e181. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02495922
- IMROZ: Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hájek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Brégeault MF, Macé S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Jun 3. Epub ahead of print. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03319667
Lenalidomide & Prednisone (RP)
RP: Revlimid (Lenalidomide) & Prednisone
Regimen variant #1, prednisone 25 mg every other day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Magarotto et al. 2016 (EMN01) | 2009-2012 | Phase 3 (E-esc) | Lenalidomide | Not reported |
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Prednisone (Sterapred) 25 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
Supportive therapy
- Aspirin or LMWH or Warfarin (Coumadin) at physician's discretion (mandatory)
28-day cycles
Regimen variant #2, prednisone 25 mg TIW
Study | Dates of enrollment | Evidence |
---|---|---|
Falco et al. 2012 | 2008-2009 | Phase 2 |
Preceding treatment
- MPR consolidation x 6
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Prednisone (Sterapred) 25 mg PO three times per week on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26
Supportive therapy
- Thromboprophylaxis: Aspirin 100 mg PO once per day, taken during lenalidomide treatment (unclear from protocol if this also means off weeks)
- Antiviral prophylaxis if history of VZV.
28-day cycles
Regimen variant #3, prednisone 50 mg every other day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gay et al. 2015 (EMN-441) | 2009-2011 | Phase 3 (E-esc) | Lenalidomide | Did not meet primary endpoint of PFS Median PFS: 37.5 vs 28.5 mo (HR 0.84, 95% CI 0.59-1.20) |
Preceding treatment
- Tandem high-dose melphalan with autologous hematopoietic stem cell transplants versus CRd consolidation
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
28-day cycles
References
- Falco P, Cavallo F, Larocca A, Rossi D, Guglielmelli T, Rocci A, Grasso M, Siez ML, De Paoli L, Oliva S, Molica S, Mina R, Gay F, Benevolo G, Musto P, Omedè P, Freilone R, Bringhen S, Carella AM, Gaidano G, Boccadoro M, Palumbo A. Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. 2013 Mar;27(3):695-701. Epub 2012 Sep 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EMN-441: Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1617-29. Epub 2015 Nov 17. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01091831
- EMN01: Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. Epub 2016 Jan 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01093196
RVD
RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
VDR: Velcade (Bortezomib), Dexamethasone, Revlimid (Lenalidomide)
VRD: Velcade (Bortezomib), Revlimid (Lenalidomide), Dexamethasone
VRd: Velcade (Bortezomib), Revlimid (Lenalidomide), low-dose dexamethasone
Regimen variant #1, 3-year course
Study | Dates of enrollment | Evidence |
---|---|---|
Nair et al. 2010 (2006-66) | 2006-11 to 2008-09 | Non-randomized |
Preceding treatment
- VTD-PACE consolidation (per Total Therapy 3 protocol)
Targeted therapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 20, then 5 mg PO once per day on days 21 to 28
- Bortezomib (Velcade) as follows:
- Cycles 1 to 13: 1 mg/m2 IV once per day on days 1, 4, 8, 11
- Cycles 14 to 39: 1 mg/m2 IV once per day on days 1, 8, 15, 22
Glucocorticoid therapy
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 13: 20 mg (route not specified) once per day on days 1 to 4, 8 to 11
- Cycles 14 to 39: 20 mg (route not specified) once per day on days 1, 8, 15, 22
28-day cycle for 39 cycles (3 years)
Regimen variant #2, Indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Richardson et al. 2010 (DFCI 06-150) | 2006-2008 | Phase 1/2 |
Preceding treatment
- Induction RVD x 4 to 8
Targeted therapy
- Lenalidomide (Revlimid) 25 mg (or previously tolerated dose) PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 (or previously tolerated dose) IV once per day on days 1 & 8
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg (or previously tolerated dose) PO once per day on days 1, 2, 8, 9
Supportive therapy
- Aspirin 81 mg or 325 mg PO once per day on days 1 to 21
- Antiviral therapy, such as Acyclovir (Zovirax) 400 mg PO once per day on days 1 to 21
- Bisphosphonate
21-day cycles
References
- 2006-66: Nair B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Szymonifka J, Hoering A, Alsayed Y, Waheed S, Crowley J, Barlogie B. Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance. Blood. 2010 May 27;115(21):4168-73. Epub 2010 Feb 2. link to original article link to PMC article PubMed
- DFCI 06-150: Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. Epub 2010 Apr 12. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00378105
- Retrospective: Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. link to original article PubMed
Thalidomide monotherapy
Regimen variant #1, 50 mg/day x 2 years
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sonneveld et al. 2012 (HOVON-65) | 2005-2008 | Phase 3 (C) | Bortezomib | Inferior PFS1 |
Sonneveld et al. 2012 (GMMG-HD4) | 2005-2008 | Phase 3 (C) | Bortezomib | Inferior PFS1 |
1In the initial publication, this arm seemed to have an overall survival disadvantage; this was no longer present in the updated report of 2017; PFS was the primary endpoint.
Note: Observed efficacy is for induction PAD, then transplant, then maintenance bortezomib compared with induction VAD, then transplant, then maintenance thalidomide. Treatment starts 4 weeks after the final autologous hematopoietic stem cell transplant. HOVON-65/GMMG-HD4 was a single phase 3 RCT but the consolidation was different by group, so is reported here as 2 distinct trials.
Preceding treatment
- HOVON-65: High-dose melphalan with autologous hematopoietic stem cell transplant consolidation
- GMMG-HD4: High-dose melphalan with tandem autologous hematopoietic stem cell transplants consolidation
Regimen variant #2, 50 mg/d, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lokhorst et al. 2009 (HOVON-50) | 2001-2005 | Phase 3 (E-esc) | See link | See link |
Wijermans et al. 2010 (HOVON 49) | 2002-2007 | Non-randomized part of phase 3 RCT |
Preceding treatment
Targeted therapy
- Thalidomide (Thalomid) 50 mg PO once per day
Supportive therapy
- HOVON 49: Bisphosphonate use recommended with Pamidronate (Aredia) or Clodronate (Bonefos); "a maximum treatment period of 2 years was recommended in patients without active disease."
- HOVON 49: During maintenance therapy, "low-dose Aspirin was advised"
Continued indefinitely
Regimen variant #3, 50 -> 100 mg/d, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morgan et al. 2010 (MRC Myeloma IX) | 2003-2007 | Phase 3 (E-esc) | Observation | Superior PFS1 (co-primary endpoint) Median PFS: 23 vs 15 mo (HR 0.69, 95% CI 0.58-0.82) |
1Reported efficacy is based on the update e-published on 2011 Oct 20.
Preceding treatment
- MRC Myeloma IX, intensive treatment pathway: High-dose melphalan & autologous hematopoietic stem cell transplant consolidation
- MRC Myeloma IX, non-intensive treatment pathway: Induction CTDa versus MP
Targeted therapy
- Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 28
- Cycle 2 onwards: 100 mg PO once per day on days 1 to 28
28-day cycles
Regimen variant #4, 100 mg/day x 3 years
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rosiñol et al. 2012 (GEM05/MENOS65) | 2006-2009 | Phase 3 (E-switch-ooc) | 1. Interferon alfa-2b | Not reported |
2. TV | Seems to have inferior PFS1 (secondary endpoint) |
1Reported efficacy for GEM05/MENOS65 is based on the 2017 update.
Preceding treatment
- High-dose melphalan & autologous HSCT consolidation
Regimen variant #5, 100 mg/d, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Palumbo et al. 2006 (GISMM2001-A) | 2002-2005 | Non-randomized part of phase 3 RCT | ||
Stewart et al. 2015 (ECOG E1A06) | 2008-2011 | Non-randomized part of phase 3 RCT | ||
Zweegman et al. 2016 (HOVON87/NMSG18) | 2009-2012 | Phase 3 (C) | Lenalidomide | Did not meet primary endpoint of PFS |
Preceding treatment
Targeted therapy
- Thalidomide (Thalomid) 100 mg PO once per day
Supportive therapy
- Per ECOG E1A06, Aspirin was required (dose not specified)
- Per ECOG E1A06, full anticoagulation was used for patients at "higher risk" for DVT
- Per ECOG E1A06, Pamidronate (Aredia) 90 mg IV once per month recommended for patients with "active bone disease"
Continued indefinitely
Regimen variant #6, 400 mg/day x 18 months
Study | Dates of enrollment | Evidence |
---|---|---|
Sahebi et al. 2006 | 2001-05 to 2004-01 | Phase 2 |
Preceding treatment
Targeted therapy
- Thalidomide (Thalomid) 50 mg PO once per day, escalated by 50 mg every week to a target dose of 400 mg PO once per day
Supportive therapy
- Bisphosphonate once per month
- Vitamin B6
18 months of treatment or 6 months past CR, whichever comes first
Regimen variant #7, 400 mg/d, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Attal et al. 2006 (IFM 99-02) | 2000-2003 | Phase 3 (E-esc) | 1. Observation 2. Pamidronate |
Superior OS |
Preceding treatment
- Induction VAD x 3 to 4, then high-dose melphalan with tandem autologous hematopoietic stem cell transplant consolidation
Targeted therapy
- Thalidomide (Thalomid) 400 mg PO once per day on days 1 to 28
Supportive therapy
- Pamidronate (Aredia) 90 mg IV once on day 1
28-day cycles
Dose and schedule modifications
- Thalidomide dose reductions to a minimum of 50 mg PO once per day were allowed
References
- GISMM2001-A: Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825-31. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00232934
- Update: Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14. Epub 2008 May 27. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Sahebi F, Spielberger R, Kogut NM, Fung H, Falk PM, Parker P, Krishnan A, Rodriguez R, Nakamura R, Nademanee A, Popplewell L, Frankel P, Ruel C, Tin R, Ilieva P, Forman SJ, Somlo G. Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant in patients with multiple myeloma. Bone Marrow Transplant. 2006 May;37(9):825-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- IFM 99-02: Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T; IFM. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15;108(10):3289-94. Epub 2006 Jul 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00222053
- Pooled update: Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, Durie BG, Harousseau JL. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences. J Clin Oncol. 2010 Mar 1;28(7):1209-14. Epub 2010 Jan 19. Erratum in: J Clin Oncol. 2010 Jul 20;28(21):3543. link to original article link to PMC article PubMed
- **RETRACTED** Abdelkefi A, Ladeb S, Torjman L, Othman TB, Lakhal A, Romdhane NB, Omri HE, Elloumi M, Belaaj H, Jeddi R, Aissaouï L, Ksouri H, Hassen AB, Msadek F, Saad A, Hsaïri M, Boukef K, Amouri A, Louzir H, Dellagi K, Abdeladhim AB; Tunisian Multiple Myeloma Study Group. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood. 2008 Feb 15;111(4):1805-10. Epub 2007 Sep 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed **RETRACTED** NCT00207805
- HOVON-50: Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00028886
- Update: van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. link to original article PubMed
- HOVON 49: Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. Epub 2010 Jun 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- MRC Myeloma IX: Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. link to original article link to PMC article PubMed ISRCTN68454111
- Update: Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, Coy NN, Cook G, Russell NH, Rudin C, Roddie H, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5;119(1):7-15. Epub 2011 Oct 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. link to original article PubMed
- GEM05/MENOS65: Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00461747
- Update: Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- HOVON-65: Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN64455289
- Subgroup analysis: Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. link to original article PubMed
- Update: Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. link to original article PubMed
- GMMG-HD4: Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN64455289
- Subgroup analysis: Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, Salwender H, Blau IW, Weisel K, Pfreundschuh M, Scheid C, Dührsen U, Lindemann W, Schmidt-Wolf IG, Peter N, Teschendorf C, Martin H, Haenel M, Derigs HG, Raab MS, Ho AD, van de Velde H, Hose D, Sonneveld P, Goldschmidt H. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26;119(4):940-8. Epub 2011 Dec 8. link to original article PubMed
- Update: Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018 Feb;32(2):383-390. Epub 2017 Jul 4. link to original article PubMed
- ECOG E1A06: Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, Rajkumar SV. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015 Sep 10;126(11):1294-301. Epub 2015 Jul 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00602641
- HOVON87/NMSG18: Zweegman S, van der Holt B, Mellqvist UH, Salomo M, Bos GM, Levin MD, Visser-Wisselaar H, Hansson M, van der Velden AW, Deenik W, Gruber A, Coenen JL, Plesner T, Klein SK, Tanis BC, Szatkowski DL, Brouwer RE, Westerman M, Leys MR, Sinnige HA, Haukås E, van der Hem KG, Durian MF, Mattijssen EV, van de Donk NW, Stevens-Kroef MJ, Sonneveld P, Waage A. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 Mar 3;127(9):1109-16. Epub 2016 Jan 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2007-004007-34
Thalidomide & Dexamethasone (TD)
TD: Thalidomide, Dexamethasone
Thal-Dex: Thalidomide, Dexamethasone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Maiolino et al. 2012 (GBRAM0001) | 2003-2008 | Phase 3 (E-esc) | Dexamethasone | Superior PFS (primary endpoint) Median PFS: 36 vs 19 mo |
Preceding treatment
Targeted therapy
- Thalidomide (Thalomid) 200 mg PO once per day
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
28-day cycle for 12 months or until disease progression
References
- BMT CTN 0102: Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; BMT CTN. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. Epub 2011 Sep 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00075829
- GBRAM0001: Maiolino A, Hungria VT, Garnica M, Oliveira-Duarte G, Oliveira LC, Mercante DR, Miranda EC, Quero AA, Peres AL, Barros JC, Tanaka P, Magalhães RP, Rego EM, Lorand-Metze I, Lima CS, Renault IZ, Braggio E, Chiattone C, Nucci M, de Souza CA; Brazilian Multiple Myeloma Study Group. Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma. Am J Hematol. 2012 Oct;87(10):948-52. Epub 2012 Jun 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01296503
Thalidomide & Prednisolone (TP)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spencer et al. 2009 (ALLG MM6) | 2002-2005 | Phase 3 (E-esc) | Prednisolone | Superior OS1 (co-primary endpoint) OS60: 66% vs 47% (HR 0.12, 95% CI 0.03-0.56) |
1Reported efficacy is based on the 2014 update.
Note: Thalidomide dose was increased only if the starting dose was tolerated.
Preceding treatment
- High-dose melphalan & auto HSCT consolidation
Targeted therapy
- Thalidomide (Thalomid) as follows:
- Cycle 1: 100 mg PO once per day on days 1 to 14, then 200 mg PO once per day on days 15 to 28
- Cycles 2 to 13: 200 mg PO once per day on days 1 to 28
Glucocorticoid therapy
- Prednisolone (Millipred) 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
28-day cycles
References
- ALLG MM6: Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, Gill DS, Horvath N, Reynolds J, Kennedy N. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009 Apr 10;27(11):1788-93. Epub 2009 Mar 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed ACTRN12607000382471
- Subgroup analysis: Ho PJ, Brown RD, Spencer A, Jeffels M, Daniher D, Gibson J, Joshua DE. Thalidomide consolidation improves progression-free survival in myeloma with normal but not up-regulated expression of fibroblast growth factor receptor 3: analysis from the Australasian Leukaemia and Lymphoma Group MM6 clinical trial. Leuk Lymphoma. 2012 Sep;53(9):1728-34. Epub 2012 Mar 13. link to original article PubMed
- Update: Kalff A, Kennedy N, Smiley A, Prince HM, Roberts AW, Bradstock K, De Abreu Lourenço R, Frampton C, Spencer A. Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study. Lancet Haematol. 2014 Dec;1(3):e112-9. Epub 2014 Dec 1. link to original article PubMed
Thalidomide & Prednisone (TP)
TP: Thalidomide & Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Stewart et al. 2013 (NCIC-CTG MY.10) | 2002-2009 | Phase 3 (E-esc) | Observation | Did not meet primary endpoint of OS OS48: 68% vs 60% (HR 0.77) |
Decreased QOL |
Preceding treatment
- High-dose melphalan with autologous HSCT consolidation
Targeted therapy
- Thalidomide (Thalomid) 200 mg PO once per day
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO once every other day
Supportive therapy
- "Bisphosphonates, histamine-2 blockers, and laxatives were recommended"
- "Anticoagulant and antiplatelet medications were not mandated"
Four years or until disease progression
References
- NCIC-CTG MY.10: Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. Epub 2013 Jan 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00049673
Bortezomib & Prednisone (VP)
VP: Velcade (Bortezomib) & Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mateos et al. 2010 (GEM2005) | 2006-2008 | Phase 3 (C) | VT | Did not meet primary endpoint of ORR |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO once every other day
Supportive therapy
- Patients with bone disease received bisphosphonates
- Prophylactic Acyclovir (Zovirax) was recommended.
3-month cycle for up to 12 cycles (3 years)
References
- GEM2005: Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00443235
- Subgroup analysis: Mateos MV, Gutiérrez NC, Martín-Ramos ML, Paiva B, Montalbán MA, Oriol A, Martínez-López J, Teruel AI, Bengoechea E, Martín A, Díaz-Mediavilla J, de Arriba F, Palomera L, Hernández JM, Sureda A, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, Fernández M, García-Sanz R, Vidriales MB, Bladé J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. Epub 2011 Sep 6. link to original article PubMed
- Update: Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. Epub 2012 Aug 13. link to original article PubMed
- Update: Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?. Blood. 2014 Sep 18;124(12):1887-93. Epub 2014 Aug 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
VT
VT: Velcade (Bortezomib) & Thalidomide
TV: Thalidomide & Velcade (Bortezomib)
Regimen variant #1, 1.3/50 x 2 y
Study | Dates of enrollment | Evidence |
---|---|---|
Palumbo et al. 2010 (GIMEMA MM-03-05) | 2006-2009 | Non-randomized part of phase 3 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Induction VMPT x 9
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once on day 1
- Thalidomide (Thalomid) 50 mg PO once per day
14-day cycle for up to 2 years or until disease progression or relapse
Regimen variant #2, 1.3/50 x 3 y
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mateos et al. 2010 (GEM2005) | 2006-2008 | Phase 3 (E-esc) | VP | Did not meet primary endpoint of ORR |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 50 mg PO once per day
Supportive therapy
- Patients with bone disease received bisphosphonates
- Prophylactic aciclovir was recommended.
- Thromboprophylaxis with either aspirin or low molecular weight heparin
3-month cycle for up to 12 cycles (3 years)
Regimen variant #3, 1.3/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rosiñol et al. 2012 (GEM05/MENOS65) | 2006-2009 | Phase 3 (E-esc) | 1. Interferon alfa-2b 2. Thalidomide |
Seems to have superior PFS1 (secondary endpoint) |
1Reported efficacy is based on the 2017 update.
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- High-dose melphalan & autologous HCT consolidation
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
3-month cycle for up to 12 cycles (3 years)
References
- GEM2005: Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00443235
- Subgroup analysis: Mateos MV, Gutiérrez NC, Martín-Ramos ML, Paiva B, Montalbán MA, Oriol A, Martínez-López J, Teruel AI, Bengoechea E, Martín A, Díaz-Mediavilla J, de Arriba F, Palomera L, Hernández JM, Sureda A, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, Fernández M, García-Sanz R, Vidriales MB, Bladé J, Lahuerta JJ, San Miguel JF. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27;118(17):4547-53. Epub 2011 Sep 6. link to original article PubMed
- Update: Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012 Sep 27;120(13):2581-8. Epub 2012 Aug 13. link to original article PubMed
- Update: Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?. Blood. 2014 Sep 18;124(12):1887-93. Epub 2014 Aug 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GIMEMA MM-03-05: Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01063179
- Post-hoc analysis: Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Subgroup analysis: Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. link to original article PubMed
- Subgroup analysis: Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. Epub 2011 Sep 27. link to original article PubMed
- Update: Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014 Mar 1;32(7):634-40. Epub 2014 Jan 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GEM05/MENOS65: Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; PETHEMA; GEM. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. Epub 2012 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00461747
- Update: Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, Granell M, Sampol M, Palomera L, González Y, Etxebeste M, Martínez-Martínez R, Hernández MT, de Arriba F, Alegre A, Cibeira M, Mateos M, Martínez-López J, Lahuerta JJ, San Miguel J, Bladé J. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017 Sep;31(9):1922-1927. Epub 2017 Jan 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Response criteria
- IMWG international uniform response criteria for multiple myeloma. (Durie et al. Leukemia 2006) PubMed
- Make note of these errors which remain in the online version of the IMWG criteria as of 7/7/2013.
- Clarification of the definition of complete response in multiple myeloma (Leukemia 2015) PubMed
- European Blood and Marrow Transplant (EBMT) criteria. (Bladé et al. Br J Hematol 1998) PubMed
Prognosis
Durie-Salmon Staging System - 1975
Composed of four factors with a modifier based on renal function
- Serum levels of monoclonal protein (only defined for IgM, IgA, and Bence-Jones)
- Number of lytic bone lesions
- Hemoglobin
- Serum calcium level
Risk stratification
- Stage I: (must meet ALL criteria)
- Hemoglobin greater than 10 g/dL
- Calcium normal or less than or equal to 12 mg/dL
- Skeletal survey with normal bone structure (scale 0) or solitary bone plasmacytoma only
- Monoclonal protein relatively small (IgG M-spike value less than 5 g/dL OR IgA M-spike value less than 3 g/dL OR urine light chain protein less than 4 g/24 hr)
- Stage II: not stage I or stage III
- Stage III: (if meets ANY of the criteria)
- Hemoglobin less than 8.5 g/dL
- Calcium greater than 12 mg/dL
- Skeletal survey with extensive skeletal destruction and major fractures
- Monoclonal protein relatively large (IgG M-spike value greater than 7 g/dL OR IgA M-spike value greater than 5 g/dL OR urine light chain protein greater than 12 g/24 hr)
Modifier
- A: relatively normal creatinine (less than 2 mg/dL)
- B: creatinine greater than or equal to 2 mg/dL
References
- Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842-54. link to original article PubMed
International Staging System (ISS) - 2005
Composed of two factors
- Serum albumin level
- Serum beta-2 microglobulin level
Risk stratification
- Stage I: Median survival of 62 months
- Beta-2 microglobulin less than 3.5 mg/l
- Albumin greater than or equal to 3.5 g/dl
- Stage II: Median survival of 44 months
- Not meeting stage I or stage III criteria
- Stage III: Median survival of 29 months
- Beta-2 microglobulin greater than or equal to 5.5 mg/l
References
- Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20;23(15):3412-20. Epub 2005 Apr 4. link to original article PubMed
- Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. Epub 2008 Oct 30. link to original article link to PMC article PubMed
IMWG consensus on risk stratification - 2013
Composed of four factors
- Serum albumin level
- Serum beta-2 microglobulin level
- Age
- Chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH)
Risk stratification
- Low risk: (must meet all criteria) Median survival of greater than 10 years
- ISS Stage I or II
- Age less than 55 years
- Absence of the following: del(17p13), t(4;14), +1q21
- Standard risk: Median survival of 7 years
- Not meeting low risk or high risk criteria
- High risk: (if meets both criteria) Median survival of 2 years
- ISS Stage II or III
- Either of the following: del(17p13) or t(4;14)
References
- Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, San Miguel J, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H; International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014 Feb;28(2):269-77. Epub 2013 Aug 26. link to original article PubMed
Revised International Staging System (R-ISS) - 2015
Composed of four factors
- Serum albumin level
- Serum beta-2 microglobulin level
- Serum LDH
- Chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH)
Risk stratification
- Low risk: 5-year overall survival = 82%
- Beta-2 microglobulin less than 3.5 mg/l
- Albumin less than or equal to 3.5 g/dl
- LDH less than the upper limit of normal range
- Absence of the following: del(17p), t(4;14), t(14;16)
- Intermediate risk: 5-year overall survival = 62%
- Not meeting low risk or high risk criteria
- High risk: (if meets ANY of the criteria) 5-year overall survival = 40%
- Beta-2 microglobulin greater than or equal to 5.5 mg/l
- LDH greater than the upper limit of normal range
- Any of the following: del(17p), t(4;14), t(14;16)
References
- Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3. link to original article link to PMC article PubMed
Miscellaneous
- Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007 Apr 15;109(8):3489-95. Epub 2007 Jan 5. link to original article PubMed
- Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, Royer B, Dib M, Voillat L, Bouscary D, Caillot D, Wetterwald M, Pegourie B, Lepeu G, Corront B, Karlin L, Stoppa AM, Fuzibet JG, Delbrel X, Guilhot F, Kolb B, Decaux O, Lamy T, Garderet L, Allangba O, Lifermann F, Anglaret B, Moreau P, Harousseau JL, Facon T. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the Intergroupe Francophone du Myélome experience. J Clin Oncol. 2013 Aug 1;31(22):2806-9. Epub 2013 Jun 24. link to original article link to PMC article PubMed