Difference between revisions of "Staging page"

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? Please go to the [[Multiple myeloma|main multiple myeloma regimen page]] to find other regimens.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=First-line therapy=
 
−
==ABCM {{#subobject:c073a5|Regimen=1}}==
 
−
ABCM: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''CNU (Carmustine), '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:79c96f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1016/0140-6736(92)90004-M MacLennan et al. 1992 (MRC Myeloma V)]
 
−
|1982-1986
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc-ic)
 
−
|[[#Melphalan_monotherapy|Melphalan]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 32 vs 24 mo
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)]
 
−
|1993-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#C-VAMP|C-VAMP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Melphalan (Alkeran)]]
 
−
</div></div>
 
−
===References===
 
−
# '''MRC Myeloma V:''' MacLennan IC, Chapman C, Dunn J, Kelly K; Medical Research Council Working Party for Leukaemia in Adults. Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis. Lancet. 1992 Jan 25;339(8787):200-5. [https://doi.org/10.1016/0140-6736(92)90004-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/1346171 PubMed]
 
−
# '''MRC Myeloma VII:''' Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. [https://doi.org/10.1056/NEJMoa022340 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12736280 PubMed] NCT00002599
 
−
# '''MRC Myeloma VIII:''' NCT00002653
 
−
==BiRd {{#subobject:4ea159|Regimen=1}}==
 
−
BiRd: '''<u>Bi</u>'''axin (Clarithromycin), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<br>C-Rd: '''<u>C</u>'''larithromycin, '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d718cd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/3/1101.long Niesvizky et al. 2007]
 
−
|2004-2006
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1038/s41408-021-00490-8 Puig et al. 2021 (GEM-CLARIDEX)]
 
−
|2015-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc-ic)
 
−
|[[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 23 vs 29 mo<br>(HR 1.29, 95% CI 0.92-1.82)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Clarithromycin (Biaxin)]] as follows:
 
−
**Cycle 1: 500 mg PO twice per day on days 2 to 28
 
−
**Cycle 2 onwards: 500 mg PO twice per day on days 1 to 28
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 40 mg PO once per day on days 1, 2, 3, 8, 15, 22
 
−
**Cycle 2 onwards: 40 mg PO once per day on days 1, 8, 15, 22
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] as follows:
 
−
**Cycle 1: 25 mg PO once per day on days 3 to 21
 
−
**Cycle 2 onwards: 25 mg PO once per day on days 1 to 21
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
*[[Omeprazole (Prilosec)]] 20 mg PO once per day
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] PO twice per day, 3 times a week
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Niesvizky R, Jayabalan DS, Christos PJ, Furst JR, Naib T, Ely S, Jalbrzikowski J, Pearse RN, Zafar F, Pekle K, Larow A, Lent R, Mark T, Cho HJ, Shore T, Tepler J, Harpel J, Schuster MW, Mathew S, Leonard JP, Mazumdar M, Chen-Kiang S, Coleman M. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood. 2008 Feb 1;111(3):1101-9. Epub 2007 Nov 7. [http://www.bloodjournal.org/content/111/3/1101.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17989313 PubMed] NCT00151203
 
−
## '''Update:''' Rossi A, Mark T, Jayabalan D, Christos P, Zafar F, Pekle K, Pearse R, Chen-Kiang S, Coleman M, Niesvizky R. BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma. Blood. 2013 Mar 14;121(11):1982-1985. Epub 2013 Jan 8. [http://www.bloodjournal.org/content/121/11/1982.full link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596960/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23299315 PubMed]
 
−
# '''Retrospective:''' Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol. 2010 Sep;85(9):664-9. [http://dx.doi.org/10.1002/ajh.21777 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956597/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20645430 PubMed]
 
−
#'''GEM-CLARIDEX:''' Puig N, Hernández MT, Rosiñol L, González E, de Arriba F, Oriol A, González-Calle V, Escalante F, de la Rubia J, Gironella M, Ríos R, García-Sánchez R, Arguiñano JM, Alegre A, Martín J, Gutiérrez NC, Calasanz MJ, Martín ML, del Carmen Couto M, Casanova M, Arnao M, Pérez-Persona E, Garzón S, González MS, Martín-Sánchez G, Ocio EM, Coleman M, Encinas C, Vale AM, Teruel AI, Cortés-Rodríguez M, Paiva B, Cedena MT, San-Miguel JF, Lahuerta JJ, Bladé J, Niesvizky R, Mateos MV. Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial. Blood Cancer J. 2021 May 21;11(5):101. [https://doi.org/10.1038/s41408-021-00490-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34021118/ PubMed] NCT02575144
 
−
==mCOP/MP {{#subobject:000cb3|Regimen=1}}==
 
−
mCOP/MP: '''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone alternating with '''<u>M</u>'''elphalan & '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9ac18d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://link.springer.com/article/10.1532/IJH97.03115 Takenaka et al. 2004 (JCOG 9301)]
 
−
|1993-1998
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#MCNU-COP.2FMP_99|MCNU-COP/MP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 350 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
 
−
*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 22 to 24
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 3, 8 to 10, 22 to 24
 
−
'''42-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''JCOG 9301:''' Takenaka T, Itoh K, Suzuki T, Utsunomiya A, Matsuda S, Chou T, Sai T, Sano M, Konda S, Ohno T, Mikuni C, Deura K, Yamada T, Mizorogi F, Nagoshi H, Tomonaga M, Hotta T, Kawano K, Tsushita K, Hirano M, Shimoyama M; Lymphoma Study Group of the Japan Clinical Oncology Group. Phase III study of ranimustine, cyclophosphamide, vincristine, melphalan, and prednisolone (MCNU-COP/MP) versus modified COP/MP in multiple myeloma: a Japan clinical oncology group study, JCOG 9301. Int J Hematol. 2004 Feb;79(2):165-73. [https://link.springer.com/article/10.1532/IJH97.03115 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15005346 PubMed]
 
−
==C-VAMP {{#subobject:f54cbe|Regimen=1}}==
 
−
C-VAMP: '''<u>C</u>'''yclophosphamide, '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethyl'''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f6679c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1046/j.1365-2141.1997.d01-2122.x Raje et al. 1997]
 
−
|1985-1994
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)]
 
−
|1993-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#ABCM|ABCM]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
''Note: A minimum of 3 cycles were given before stem cell harvest.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg IV once per day on days 1, 8, 15
 
−
**Cyclophosphamide was omitted in patients with a serum creatinine greater than 3.4 mg/dL
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Methylprednisolone (Solumedrol)]] 1000 mg/m<sup>2</sup> (maximum dose of 1500 mg) IV or PO once per day on days 1 to 5
 
−
 
−
'''21-day cycles, given until maximal response was achieved'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*MRC Myeloma VII: [[Stem_cell_mobilization#Cyclophosphamide_.26_G-CSF|Cyclophosphamide & G-CSF stem cell mobilization]], then [[#Melphalan_.26_Methylprednisolone.2C_then_auto_HSCT|high-dose melphalan & methylprednisolone with auto HSCT]]
 
−
</div></div>
 
−
===References===
 
−
# Raje N, Powles R, Kulkarni S, Milan S, Middleton G, Singhal S, Mehta J, Millar B, Viner C, Raymond J, Treleaven J, Cunningham D, Gore M. A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma. Br J Haematol. 1997 Apr;97(1):153-60. [https://doi.org/10.1046/j.1365-2141.1997.d01-2122.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9136958 PubMed]
 
−
# '''MRC Myeloma VII:''' Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. [https://doi.org/10.1056/NEJMoa022340 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12736280 PubMed] NCT00002599
 
−
==Cyclophosphamide monotherapy {{#subobject:02041e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:dc52bc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/1164446 Korst et al. 1964]
 
−
|NR-1963
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 2 mg/kg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Korst DR, Clifford GO, Fowler WM, Louis J, Will J, Wilson HE. Multiple myeloma II: analysis of cyclophosphamide therapy in 165 patients. JAMA. 1964 Sep 7;189:758-62. [https://jamanetwork.com/journals/jama/article-abstract/1164446 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14175647 PubMed]
 
−
==CVP {{#subobject:fdb4g3|Regimen=1}}==
 
−
CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<br>VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f18632|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.1986.4.8.1227 Durie et al. 1986 (SWOG S7927/S7928)]
 
−
|1979-1982
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VMCP.2FVBAP|VMCP/VBAP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 180 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
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S7927/S7928:''' Durie BG, Dixon DO, Carter S, Stephens R, Rivkin S, Bonnet J, Salmon SE, Dabich L, Files JC, Costanzi JJ. Improved survival duration with combination chemotherapy induction for multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1986 Aug;4(8):1227-37. [https://doi.org/10.1200/JCO.1986.4.8.1227 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3525768 PubMed]
 
−
==Dexamethasone monotherapy {{#subobject:b86fb2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 35-day cycles {{#subobject:05800b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://annals.org/aim/fullarticle/700565/high-dose-glucocorticoid-treatment-resistant-myeloma Alexanian et al. 1986]
 
−
|1983-1985
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|[http://www.bloodjournal.org/content/80/4/887 Alexanian et al. 1992]
 
−
|1989-1991
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
'''35-day cycle for 3 cycles (Alexanian et al. 1992) or until maximal response (Alexanian et al. 1986)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Alexanian et al. 1992:
 
−
**Responders: [[#Interferon_alfa_monotherapy|Interferon alfa]] maintenance
 
−
**Non-responders: unclear from manuscript
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite with 35-day induction cycles {{#subobject:05800b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC3031379/ Zonder et al. 2010 (SWOG S0232)]
 
−
|2004-2007
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Len-Dex]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for transplantation-ineligible or -denying patients who had to have symptomatic disease with a measurable M-protein, be at least 18 years old, and have a performance status less than 3 (unless resulting from myeloma). Note that the first 3 cycles, termed "induction" in the protocol, were 35-day cycles. 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:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 3: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 4 onwards: 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 325 mg PO once per day unless already on anticoagulation therapy
 
−
'''35-day cycle for 3 cycles, then 28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, indefinite with 28-day induction cycles {{#subobject:21bfc9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC3904367/ Rajkumar et al. 2008 (THAL-MM-003)]
 
−
|2003-2005
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#Thalidomide_.26_Dexamethasone_.28TD.29|TD]]
 
−
|style="background-color:#d73027"|Inferior TTP
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with previously untreated symptomatic multiple myeloma, bone marrow plasmacytosis (greater than or equal to 10% plasma cells or sheets of plasma cells) or a biopsy-proven plasmacytoma, and measurable disease defined as serum monoclonal protein more than 1 g/dL and/or urine monoclonal protein greater than or equal to 200 mg/24 h. 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:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, indefinite with alternating dexamethasone intensity {{#subobject:bb3ebb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.03.0221 Rajkumar et al. 2005 (ECOG E1A00)]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#Thalidomide_.26_Dexamethasone_.28TD.29|TD]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior RR
 
−
|style="background-color:#1a9850"|Superior toxicity
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with previously untreated symptomatic multiple myeloma, bone marrow plasmacytosis (greater than or equal to 10% plasma cells or sheets of plasma cells) or a biopsy-proven plasmacytoma, and measurable disease defined as serum monoclonal protein more than 1 g/dL and/or urine monoclonal protein greater than or equal to 200 mg/24 h.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Odd-numbered cycles: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Even-numbered cycles: 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 12 cycles total {{#subobject:5be1f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/4/1292.long Facon et al. 2005 (IFM 95-01)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
−
|1. [[#DEX-IFN|DEX-IFN]]<br>2. [[#Melphalan_.26_Prednisone_.28MP.29|MP]]<br> 3. [[#M-DEX|M-DEX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients aged between 65 and 75 years and fulfilling a diagnosis of stage II or III MM according to the [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie and Salmon criteria]]. Some stage I patients were allowed; see text for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycles 3 to 12: 40 mg PO once per day on days 1 to 4
 
−
'''42-day cycle for 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Alexanian R, Barlogie B, Dixon D. High-dose glucocorticoid treatment of resistant myeloma. Ann Intern Med. 1986 Jul;105(1):8-11. [http://annals.org/aim/fullarticle/700565/high-dose-glucocorticoid-treatment-resistant-myeloma link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3717812 PubMed]
 
−
# Alexanian R, Dimopoulos MA, Delasalle K, Barlogie B. Primary dexamethasone treatment of multiple myeloma. Blood. 1992 Aug 15;80(4):887-90. [http://www.bloodjournal.org/content/80/4/887 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1498331 PubMed]
 
−
# Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. [http://www.bloodjournal.org/content/107/4/1292.long link to original paper] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16174762 PubMed]
 
−
# '''ECOG E1A00:''' Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; [[Study_Groups#ECOG|ECOG]]. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006 Jan 20;24(3):431-6. Epub 2005 Dec 19. [https://doi.org/10.1200/jco.2005.03.0221 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16365178 PubMed] NCT00033332
 
−
# '''THAL-MM-003:''' Rajkumar SV, Rosiñol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, Olesnyckyj M, Yu Z, Knight R, Zeldis JB, Bladé J. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008 May 1;26(13):2171-7. Epub 2008 Mar 24. [https://doi.org/10.1200/jco.2007.14.1853 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18362366 PubMed] NCT00057564
 
−
# '''SWOG S0232:''' Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore DF Sr, Whittenberger BF, Abidi MH, Durie BG, Barlogie B; [[Study_Groups#SWOG|SWOG]]. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood. 2010 Dec 23;116(26):5838-41. Epub 2010 Sep 27. [http://www.bloodjournal.org/content/116/26/5838.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031379/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20876454 PubMed] NCT00064038
 
−
==DEX-IFN {{#subobject:144646|Regimen=1}}==
 
−
'''<u>DEX</u>'''amethasone, '''<u>I</u>'''nter'''<u>F</u>'''ero'''<u>N</u>''' alfa-2b
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8cae34|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/4/1292.long Facon et al. 2005 (IFM 95-01)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
−
|1. [[#Dexamethasone_monotherapy|Dexamethasone]]<br>2. [[#Melphalan_.26_Prednisone_.28MP.29|MP]]<br> 3. [[#M-DEX|M-DEX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients aged between 65 and 75 years and fulfilling a diagnosis of stage II or III MM according to the [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie and Salmon criteria]]. Some stage I patients were allowed; see text for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycles 3 to 12: 40 mg PO once per day on days 1 to 4
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2b (Intron-A)]] 3,000,000 units SC 3 times per week; start with dexamethasone and stop on on day 42 of the last cycle of dexamethasone
 
−
'''42-day cycle for 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. [http://www.bloodjournal.org/content/107/4/1292.long link to original paper] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16174762 PubMed]
 
−
==EDAP {{#subobject:0464d1|Regimen=1}}==
 
−
EDAP: '''<u>E</u>'''toposide, '''<u>D</u>'''examethasone, '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ddbc95|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/89/3/789.long Barlogie et al. 1997 (Total Therapy 1)]
 
−
|1990-1994
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
''Note: This was given as a component of Total Therapy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]]
 
−
*[[Cytarabine (Ara-C)]]
 
−
*[[Cisplatin (Platinol)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div></div>
 
−
===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. [http://www.bloodjournal.org/content/89/3/789.long 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. [http://www.bloodjournal.org/content/93/1/55.long link to original article] '''contains dosing details in manuscript''' [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. [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]
 
−
==Lenalidomide & Dexamethasone (RD) {{#subobject:18f3d0|Regimen=1}}==
 
−
RD: '''<u>R</u>'''evlimid (Lenalidomide) & high-dose '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:52864a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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(09)70284-0 Rajkumar et al. 2009 (ECOG E4A03)]
 
−
|2004-2006
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#Lenalidomide_.26_Dexamethasone_.28Rd.29|Rd]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|}
 
−
''Note: This is the high-dose dexamethasone arm, and was intended for patients with previously untreated symptomatic multiple myeloma, bone marrow plasmacytosis (greater than or equal to 10% plasma cells or sheets of plasma cells) or a biopsy-proven plasmacytoma, and measurable disease defined as serum monoclonal protein more than 1 g/dL and/or urine monoclonal protein greater than or equal to 200 mg/24 h.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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 to 4, 9 to 12, 17 to 20
 
−
====Supportive therapy====
 
−
*One of the following bisphosphonates:
 
−
**[[Pamidronate (Aredia)]] 90 mg IV over 2 to 4 hours once on day 1
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV over 15 minutes once on day 1
 
−
*Thromboprophylaxis mandatory (added mid-protocol after excess rates of DVT)
 
−
'''28-day cycle for 4 cycles (see below)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responding patients could choose after 4 cycles to proceed to [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|high-dose melphalan with autologous hematopoietic stem cell transplant]] or to continue RD until progression of disease or intolerable toxicity
 
−
*Non-responders were transitioned to [[Multiple_myeloma,_induction#Thalidomide_.26_Dexamethasone_.28TD.29|Thal-Dex]] (details not described)
 
−
</div></div>
 
−
===References===
 
−
# '''ECOG E4A03:''' Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; [[Study_Groups#ECOG|ECOG]]. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010 Jan;11(1):29-37. Epub 2009 Oct 21. Erratum in: Lancet Oncol. 2010 Jan;11(1):14. [https://doi.org/10.1016/S1470-2045(09)70284-0 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042271/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19853510 PubMed] NCT00098475
 
−
## '''Subgroup analysis:''' Jacobus SJ, Kumar S, Uno H, Van Wier SA, Ahmann GJ, Henderson KJ, Callander NS, Williams ME, Siegel DS, Greipp PR, Rajkumar SV, Fonseca R. Impact of high-risk classification by FISH: an eastern cooperative oncology group (ECOG) study E4A03. Br J Haematol. 2011 Nov;155(3):340-8. Epub 2011 Sep 9. [https://doi.org/10.1111/j.1365-2141.2011.08849.x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192237/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21902684 PubMed]
 
−
==Melphalan monotherapy {{#subobject:bb5296|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3d57a4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://science.sciencemag.org/content/148/3668/376 Bergsagel et al. 1965]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/30/1/74.long Hoogstraten et al. 1967]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/343797 Rivers & Patno 1969]
 
−
|1960-1962
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_monotherapy|Cyclophosphamide]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/347060 Hoogstraten et al. 1969a]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]]
 
−
</div></div>
 
−
===References===
 
−
# Bergsagel DE, Migliore PJ, Griffith KM. Myeloma proteins and the clinical response to melphalan therapy. Science. 1965 Apr 16;148(3668):376-7. [http://science.sciencemag.org/content/148/3668/376 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14261530 PubMed]
 
−
# Hoogstraten B, Sheehe PR, Cuttner J, Cooper T, Kyle RA, Oberfield RA, Townsend SR, Harley JB, Hayes DM, Costa G, Holland JF. Melphalan in multiple myeloma. Blood. 1967 Jul;30(1):74-83. [http://www.bloodjournal.org/content/30/1/74.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/6028709 PubMed]
 
−
# Rivers SL, Patno ME. Cyclophosphamide vs melphalan in treatment of plasma cell myeloma. JAMA. 1969 Feb 17;207(7):1328-34. [https://jamanetwork.com/journals/jama/article-abstract/343797 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4179565 PubMed]
 
−
# Hoogstraten B, Costa J, Cuttner J, Forcier J, Leone LA, Harley JB, Glidewell OJ. Intermittent melphalan therapy in multiple myeloma. JAMA. 1969 Jul 14;209(2):251-3. [https://jamanetwork.com/journals/jama/article-abstract/347060 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5819231 PubMed]
 
−
==M-DEX {{#subobject:82022a|Regimen=1}}==
 
−
M-DEX: '''<u>M</u>'''elphalan & '''<u>DEX</u>'''amethasone
 
−
<br>MD: '''<u>M</u>'''elphalan & '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 0.25/40 {{#subobject:decd99|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/4/1292.long Facon et al. 2005 (IFM 95-01)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|1. [[#Dexamethasone_monotherapy|Dexamethasone]]<br>2. [[#Melphalan_.26_Prednisone_.28MP.29|MP]]<br>3. [[#DEX-IFN|DEX-IFN]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients aged between 65 and 75 years and fulfilling a diagnosis of stage II or III MM according to the [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie and Salmon criteria]]. Some stage I patients were allowed; see text for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycles 3 to 12: 40 mg PO once per day on days 1 to 4
 
−
'''42-day cycle for 12 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 9/20 {{#subobject:edc48a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1365-2141.2004.05186.x Hernández et al. 2004 (MM-PETHEMA 96)]
 
−
|1997-NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Melphalan_.26_Prednisone_.28MP.29|MP]]
 
−
|style="background-color:#ffffbf"|Did not meet endpoints of ORR/OS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its endpoints; included here because other variants of this regimen have demonstrated comparative superiority.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 9 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 9 to 12
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MM-PETHEMA 96:''' Hernández JM, García-Sanz R, Golvano E, Bladé J, Fernandez-Calvo J, Trujillo J, Soler JA, Gardella S, Carbonell F, Mateo G, San Miguel JF. Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma. Br J Haematol. 2004 Oct;127(2):159-64. [https://doi.org/10.1111/j.1365-2141.2004.05186.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15461621 PubMed]
 
−
# '''IFM 95-01:''' Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. [http://www.bloodjournal.org/content/107/4/1292.long link to original paper] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16174762 PubMed]
 
−
==Melphalan & Prednisone (MP) {{#subobject:4d7e74|Regimen=1}}==
 
−
MP: '''<u>M</u>'''elphalan & '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, melphalan 0.15 mg/kg {{#subobject:b656fc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1600-0609.1985.tb02822.x Hansen et al. 1985]
 
−
|1979-1983
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#VMP_.28Vincristine.29_99|VMP (Vincristine)]]<br>2. [[#VBMCP|VBCMP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.15 mg/kg PO once per day on days 1 to 7
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] as follows:
 
−
**Cycle 1: 0.6 mg/kg PO once per day on days 1 to 14
 
−
**Cycle 2 onwards: 0.3 mg/kg PO once per day on days 1 to 7
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, melphalan 0.18 mg/kg {{#subobject:c04958|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1056/NEJMoa1112704 Palumbo et al. 2012 (MM-015)]
 
−
|rowspan=2|2007-2008
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[Multiple_myeloma,_induction#MPR|MPR]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
−
|-
 
−
|2. [[Multiple_myeloma,_induction#MPR|MPR-R]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with symptomatic, measurable, newly diagnosed multiple myeloma who were not candidates for transplantation (greater than or equal to 65 years of age).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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
 
−
====Supportive therapy====
 
−
*Thromboprophylaxis: [[Aspirin]] 75 to 100 mg PO once per day
 
−
'''28-day cycle for 9 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, melphalan 0.2 mg/kg {{#subobject:4ccbf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2008.21.0948 Hulin et al. 2009 (IFM 01/01)]
 
−
|2002-2006
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#MPT|MPT]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients who had stage II or III newly diagnosed multiple myeloma according to the [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie-Salmon criteria]] and were at least 75 years of age. Certain stage I patients were allowed; see text for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.2 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
 
−
'''42-day cycle for 12 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, melphalan 0.25 mg/kg x 4 d/cycle, prednisone 2 mg/kg {{#subobject:2ac5f4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://jama.jamanetwork.com/article.aspx?articleid=346198 Alexanian et al. 1969 (SWG01)]
 
−
|1965-1968
 
−
| style="background-color:#91cf61" |Non-randomized (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/epdf/10.1002/1097-0142%28197208%2930%3A2%3C382%3A%3AAID-CNCR2820300213%3E3.0.CO%3B2-C Alexanian et al. 1972]
 
−
|1968-1971
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Stub#MPP|MPP]]
 
−
|style="background-color:#ffffbf"|Did not meet endpoints of DOR/OS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/4/1292.long Facon et al. 2005 (IFM 95-01)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#Dexamethasone_monotherapy|Dexamethasone]]<br>2. [[#M-DEX|M-DEX]]<br> 3. [[#DEX-IFN|DEX-IFN]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|rowspan="2"|[https://doi.org/10.1016/S0140-6736(07)61537-2 Facon et al. 2007 (IFM 99-06)]
 
−
|rowspan=2|2000-2005
 
−
|rowspan="2" style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[Multiple_myeloma,_induction#MPT|MPT]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|2. [[#VAD|VAD]], then [[#Melphalan_monotherapy_99|MEL100]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: In IFM 95-01 this regimen was intended for patients aged between 65 and 75 years and fulfilling a diagnosis of stage II or III MM according to the [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie and Salmon criteria]]. Some stage I patients were allowed; see text for details. In IFM 99-06 this regimen was intended for patients with newly diagnosed multiple myeloma aged 65 to 75 years. 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:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.25 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
 
−
'''42-day cycle for 12 cycles (IFM 95-01 & IFM 99-06) or indefinitely (SWG01)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, melphalan 0.25 mg/kg x 4 d/cycle, flat dose prednisone {{#subobject:9f4cad|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://annals.org/aim/article-abstract/709373/interferon-2b-added-melphalan-prednisone-initial-maintenance-therapy-multiple-myeloma Hjorth et al. 1996]
 
−
|1990-1992
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#MP_.26_Interferon_alfa-2b_99|MP & IFN alfa-2b]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/116/9/1405.long Waage et al. 2010 (NMSG12)]
 
−
|2002-2007
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#MPT|MPT]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: In NMSG12, this regimen was intended for patients with previously untreated symptomatic MM, who were not eligible for high-dose treatment with autologous stem cell support.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 4
 
−
'''42-day cycles'''
 
−
''Treatment was continued until plateau phase.''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, melphalan 0.25 mg/kg x 5 d/cycle {{#subobject:f53710|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2009.26.1610 Wijermans et al. 2010 (HOVON 49)]
 
−
|2002-2007
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#MPT|MP-T]]
 
−
|style="background-color:#fee08b"|Might have inferior OS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with previously untreated MM older than age 65 years.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 5
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Bisphosphonate use recommended with [[Pamidronate (Aredia)]] or [[Clodronate (Bonefos)]]; "a maximum treatment period of 2 years was recommended in patients without active disease."
 
−
'''28-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, melphalan 4 mg/m<sup>2</sup> {{#subobject:1be67b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/S0140-6736(06)68338-4 Palumbo et al. 2006 (GISMM2001-A)]
 
−
|2002-2005
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#MPT|MPT]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with newly diagnosed multiple myeloma aged 60 to 85 years.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 4 mg/m<sup>2</sup> PO once per day on days 1 to 7
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 7
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #8, melphalan 9 mg/m<sup>2</sup> x 8 {{#subobject:d3bee4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa0801479 San Miguel et al. 2008 (VISTA)]
 
−
|2004-2006
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#VMP|VMP]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with newly diagnosed, untreated, symptomatic, measurable myeloma who were not candidates for high-dose therapy plus stem-cell transplantation because of age (greater than or equal to 65 years) or coexisting conditions.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''42-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #9, melphalan 9 mg/m<sup>2</sup> x 9 {{#subobject:d3hgr4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1600-0609.2010.01524.x Beksac et al. 2010 (TMSG-2005-001)]
 
−
|2006-2009
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#MPT|MPT]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior ORR
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients with newly diagnosed, untreated, symptomatic, measurable myeloma who were not candidates for high-dose therapy plus stem-cell transplantation because of age (greater than or equal to 65 years) or coexisting conditions.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''42-day cycle for 9 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #10, melphalan 9 mg/m<sup>2</sup> x 12 {{#subobject:fhg718|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1365-2141.2006.06405.x Shustik et al. 2007 (NCIC-CTG MY.7)]
 
−
|1995-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#M-DEX|MD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 9 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 4
 
−
'''28-day cycle for 12 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Dexamethasone_monotherapy_2|Dexamethasone]] maintenance versus [[Multiple_myeloma_-_null_regimens#Observation|no further treatment]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #11, melphalan 9 mg/m<sup>2</sup>, indefinite {{#subobject:f4eda8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJM197910043011402 Bergsagel et al. 1979]
 
−
|1973-1977
 
−
| style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#B.2FC.2FM_99|B/C/M]]<br>2. [[#BCM_99|BCM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2004.05186.x Hernández et al. 2004 (MM-PETHEMA 96)]
 
−
|1997-NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#M-DEX|MD]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 9 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] by the following study-specific criteria:
 
−
**Bergsagel et al. 1979: 100 mg PO once per day on days 1 to 4
 
−
**Hernández et al. 2004: 60 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #12, melphalan 15 mg/m<sup>2</sup> {{#subobject:8f8471|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1007/s00432-005-0074-4 Pönisch et al. 2006]
 
−
|1994-1999
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#BP_88|BP]]
 
−
|style="background-color:#d73027"|Inferior TTF
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 15 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg IV or PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SWG01:''' Alexanian R, Haut A, Khan AU, Lane M, McKelvey EM, Migliore PJ, Stuckey WJ Jr, Wilson HE. Treatment for multiple myeloma: combination chemotherapy with different melphalan dose regimens. JAMA. 1969 Jun 2;208(9):1680-5. [http://jama.jamanetwork.com/article.aspx?articleid=346198 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/5818682 PubMed]
 
−
# Alexanian R, Bonnet J, Gehan E, Haut A, Hewlett J, Lane M, Monto R, Wilson H. Combination chemotherapy for multiple myeloma. Cancer. 1972 Aug;30(2):382-9. [https://doi.org/epdf/10.1002/1097-0142%28197208%2930%3A2%3C382%3A%3AAID-CNCR2820300213%3E3.0.CO%3B2-C link to original article] [https://pubmed.ncbi.nlm.nih.gov/5051662 PubMed]
 
−
# Bergsagel DE, Bailey AJ, Langley GR, MacDonald RN, White DF, Miller AB. The chemotherapy on plasma-cell myeloma and the incidence of acute leukemia. N Engl J Med. 1979 Oct 4;301(14):743-8. [https://doi.org/10.1056/NEJM197910043011402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/481481 PubMed]
 
−
# Hansen OP, Clausen NA, Drivsholm A, Laursen B. Phase III study of intermittent 5-drug regimen (VBCMP) versus intermittent 3-drug regimen (VMP) versus intermittent melphalan and prednisone (MP) in myelomatosis. Scand J Haematol. 1985 Nov;35(5):518-24. [https://doi.org/10.1111/j.1600-0609.1985.tb02822.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/3911373 PubMed]
 
−
# Hjorth M, Westin J, Dahl IMS, Gimsing P, Hippe E, Holmberg E, Lamvik J, Lanng Nielsen J, Lofvenberg E, Palva IP, Rodjer S, Talstad I, Turesson I, Wisloff F, Zador G; Nordic Myeloma Study Group. Interferon-alpha 2b added to melphalan-prednisone for initial and maintenance therapy in multiple myeloma: a randomized, controlled trial. Ann Intern Med. 1996 Jan 15;124(2):212-22. [http://annals.org/aim/article-abstract/709373/interferon-2b-added-melphalan-prednisone-initial-maintenance-therapy-multiple-myeloma link to original article] [https://pubmed.ncbi.nlm.nih.gov/8533996 PubMed]
 
−
# '''Review:''' Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol. 1998 Dec;16(12):3832-42. [https://doi.org/10.1200/jco.1998.16.12.3832 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9850028 PubMed]
 
−
# '''MM-PETHEMA 96:''' Hernández JM, García-Sanz R, Golvano E, Bladé J, Fernandez-Calvo J, Trujillo J, Soler JA, Gardella S, Carbonell F, Mateo G, San Miguel JF. Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma. Br J Haematol. 2004 Oct;127(2):159-64. [https://doi.org/10.1111/j.1365-2141.2004.05186.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15461621 PubMed]
 
−
# '''IFM 95-01:''' Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. [http://www.bloodjournal.org/content/107/4/1292.long link to original paper] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16174762 PubMed]
 
−
# '''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16530576 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. [http://www.bloodjournal.org/content/112/8/3107.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18505783 PubMed]
 
−
# Pönisch W, Mitrou PS, Merkle K, Herold M, Assmann M, Wilhelm G, Dachselt K, Richter P, Schirmer V, Schulze A, Subert R, Harksel B, Grobe N, Stelzer E, Schulze M, Bittrich A, Freund M, Pasold R, Friedrich T, Helbig W, Niederwieser D; East German Study Group of Hematology and Oncology. Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006 Apr;132(4):205-12. Epub 2006 Jan 10. [https://doi.org/10.1007/s00432-005-0074-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16402269 PubMed]
 
−
# '''NCIC-CTG MY.7:''' Shustik C, Belch A, Robinson S, Rubin SH, Dolan SP, Kovacs MJ, Grewal KS, Walde D, Barr R, Wilson J, Gill K, Vickars L, Rudinskas L, Sicheri DA, Wilson K, Djurfeldt M, Shepherd LE, Ding K, Meyer RM. A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7. Br J Haematol. 2007 Jan;136(2):203-11. [https://doi.org/10.1111/j.1365-2141.2006.06405.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17233817/ PubMed] NCT00002678
 
−
# '''IFM 99-06:''' Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, Renaud M, Harousseau JL, Guillerm G, Chaleteix C, Dib M, Voillat L, Maisonneuve H, Troncy J, Dorvaux V, Monconduit M, Martin C, Casassus P, Jaubert J, Jardel H, Doyen C, Kolb B, Anglaret B, Grosbois B, Yakoub-Agha I, Mathiot C, Avet-Loiseau H; Intergroupe Francophone du Myélome. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007 Oct 6;370(9594):1209-18. [https://doi.org/10.1016/S0140-6736(07)61537-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17920916 PubMed] content property of [http://hemonc.org HemOnc.org] NCT00367185
 
−
# '''VISTA:''' San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG; VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28;359(9):906-17. [https://doi.org/10.1056/NEJMoa0801479 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18753647 PubMed] NCT00111319
 
−
## '''Update:''' Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Esseltine DL, Liu K, Cakana A, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1;28(13):2259-66. Epub 2010 Apr 5. [https://doi.org/10.1200/jco.2009.26.0638 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20368561 PubMed]
 
−
## '''Update:''' San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Delforge M, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Deraedt W, Cakana A, van de Velde H, Richardson PG. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013 Feb 1;31(4):448-55. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.41.6180 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23233713 PubMed]
 
−
<!-- Presented in part in abstract format at the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007; XIth International Myeloma Workshop, Kos Island, Greece, June 25-30, 2007; and the American Society of Hematology, Atlanta, GA, December 8-11, 2007. -->
 
−
# '''IFM 01/01:''' Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, Dib M, Guillerm G, Salles B, Eschard JP, Lenain P, Casassus P, Azaïs I, Decaux O, Garderet L, Mathiot C, Fontan J, Lafon I, Virion JM, Moreau P. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009 Aug 1;27(22):3664-70. Epub 2009 May 18. [https://doi.org/10.1200/jco.2008.21.0948 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19451428 PubMed] NCT00644306
 
−
# '''NMSG12:''' Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Björkstrand B, Carlson K, Dahl IM, Forsberg K, Gulbrandsen N, Haukås E, Hjertner O, Hjorth M, Karlsson T, Knudsen LM, Nielsen JL, Linder O, Mellqvist UH, Nesthus I, Rolke J, Strandberg M, Sørbø JH, Wisløff F, Juliusson G, Turesson I; Nordic Myeloma Study Group. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010 Sep 2;116(9):1405-12. Epub 2010 May 6. [http://www.bloodjournal.org/content/116/9/1405.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20448107 PubMed] NCT00218855
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20516439 PubMed] ISRCTN90692740
 
−
# '''TMSG-2005-001:''' Beksac M, Haznedar R, Firatli-Tuglular T, Ozdogu H, Aydogdu I, Konuk N, Sucak G, Kaygusuz I, Karakus S, Kaya E, Ali R, Gulbas Z, Ozet G, Goker H, Undar L. Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol. 2011 Jan;86(1):16-22. Epub 2010 Nov 22. [https://doi.org/10.1111/j.1600-0609.2010.01524.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20942865 PubMed] NCT00934154
 
−
# '''Meta-analysis:''' Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksaç M, Bringhen S, Mary JY, Gimsing P, Termorshuizen F, Haznedar R, Caravita T, Moreau P, Turesson I, Musto P, Benboubker L, Schaafsma M, Sonneveld P, Facon T; Nordic Myeloma Study Group; Italian Multiple Myeloma Network; Turkish Myeloma Study Group; HOVON; Intergroupe Francophone du Myélome; European Myeloma Network. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011 Aug 4;118(5):1239-47. Epub 2011 Jun 13. [http://www.bloodjournal.org/content/118/5/1239.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/21670471 PubMed]
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22571200 PubMed] NCT00405756
 
−
==MP (Prednisolone) {{#subobject:4d6u64|Regimen=1}}==
 
−
MP: '''<u>M</u>'''elphalan & '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, melphalan 0.25 mg/kg {{#subobject:9f4u0z|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1600-0609.1993.tb01597.x Keldsen et al. 1993]
 
−
|1987-1989
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#NOP_99|NOP]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 to 200 mg PO once per day on days 1 to 4
 
−
'''28-day cycle for 13 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, melphalan 7 mg/m<sup>2</sup> {{#subobject:e724e2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC3639680/ Morgan et al. 2010 (MRC Myeloma IX)]
 
−
|2003-2007
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#CTD|CTDa]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|}
 
−
''Note: This is a nonintensive treatment pathway, as determined by performance status, informed discussion, and patient preference.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 7 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*Patients in the study were randomized to a bisphosphonate and received one of the following until progression:
 
−
**[[Clodronate (Bonefos)|Sodium clodronate (Bonefos)]] 1600 mg PO once per day
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV once every 21 to 28 days
 
−
'''28-day cycle for 6 to 9 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_monotherapy|Thalidomide]] maintenance versus [[Multiple_myeloma_-_null_regimens#Observation|no further treatment]]
 
−
</div></div>
 
−
===References===
 
−
# Keldsen N, Bjerrum OW, Dahl IM, Drivsholm A, Ellegaard J, Gadeberg O, Gimsing P, Grønvold T, Hansen MM, Hippe E, Lamvik J, Ly B, Skarbøvik A, Talstad I, Thorling K, Wesenberg K, Wisløff F; Nordic Myeloma Study Group. Multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP regimen) versus melphalan and prednisolone: a phase III study. Eur J Haematol. 1993 Aug;51(2):80-5. [https://doi.org/10.1111/j.1600-0609.1993.tb01597.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8370422 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://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. [http://www.bloodjournal.org/content/118/5/1231.long link to original article] '''contains dosing details in manuscript''' [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. [http://www.bloodjournal.org/content/119/1/7.long link to original article] '''contains dosing details in manuscript''' [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. [http://www.haematologica.org/content/97/3/442.long link to original article] '''contains dosing details in manuscript''' [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. [http://clincancerres.aacrjournals.org/content/19/21/6030.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23995858 PubMed]
 
−
#'''RHG-MM97:''' NCT00003603
 
−
==VAD {{#subobject:9c9b6b|Regimen=1}}==
 
−
VAD: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<br>VAd: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 0.4/9/40 x 3 (bolus doxorubicin & vincristine, dex 12 days/cycle) {{#subobject:b60197|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2011.39.6820 Sonneveld et al. 2012 (HOVON-65/GMMG-HD4)]
 
−
|2005-2008
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#PAD|PAD]]
 
−
|style="background-color:#d73027"|Inferior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Observed efficacy is for induction PAD, then transplant, then maintenance bortezomib compared with induction VAD, then transplant, then maintenance thalidomide.''<br>
 
−
''Note: This regimen was intended for patients 18 to 65 years of age with newly diagnosed MM, [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie-Salmon stage]] II to III, [[#ECOG_performance_status_.28WHO.2FZubrod_score.29|WHO performance status]] 0 to 2, or WHO 3 when caused by MM. Stem cells collected 4 to 6 weeks after induction therapy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
====Supportive therapy====
 
−
*One of the following bisphosphonates recommended:
 
−
**[[Pamidronate (Aredia)]] 90 mg IV once every 4 to 6 weeks x at least 2 years
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV once every 4 to 6 weeks x at least 2 years
 
−
**[[Ibandronate (Boniva)]] 6 mg IV once every 4 to 6 weeks x at least 2 years
 
−
*"Prophylactic antibiotics" (no further specifics) during induction therapy
 
−
*Erythropoietin and pain medications at physician discretion
 
−
*One of the following for Herpes zoster prophylaxis throughout bortezomib induction:
 
−
**[[Acyclovir (Zovirax)]] 800 mg/day PO (did not specify whether taken once per day or as a divided twice per day dose)
 
−
**[[Valacyclovir (Valtrex)]] 1000 mg/day PO (did not specify whether taken once per day or as a divided twice per day dose)
 
−
'''28-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*HOVON-65: [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|Single autologous hematopoietic cell transplant]]
 
−
*GMMG-HD4: [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|Tandem autologous hematopoietic cell transplant]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 0.4/9/40 x 4 (CI doxorubicin, bolus vincristine, dex 12 days/cycle in cycles 1 & 2) {{#subobject:a91f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2009.27.9158 Harousseau et al. 2010 (IFM 2005-01)]
 
−
|2005-2008
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#Bortezomib_.26_Dexamethasone_.28VD.29|VD]]
 
−
|style="background-color:#fee08b"|Might have inferior PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients age less than or equal to 65 years with untreated symptomatic MM with measurable paraprotein in serum (greater than 1.0 g/dL) or urine (greater than 0.2 g/24 h).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 3 onwards: 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*One of the following, until first transplant:
 
−
**[[Pamidronate (Aredia)]] 90 mg IV once on day 1
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV once on day 1
 
−
*"Antibiotics, antifungal agents, and antiviral prophylaxis in accordance with local practice."
 
−
'''28-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Multiple_myeloma,_consolidation_and_maintenance#DCEP|DCEP]] consolidation versus [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|high-dose melphalan with autologous hematopoietic cell transplant]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 0.4/9/40 (CI doxorubicin & vincristine, dex 4 days/cycle) {{#subobject:89ca72|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/full/10.1111/j.1365-2141.2004.05127.x Cook et al. 2004 (WOS MM1)]
 
−
|1996-2002
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Z-Dex_99|Z-Dex]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|[http://www.bloodjournal.org/content/108/10/3289.long Attal et al. 2006 (IFM 99-02)]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.21662 Rifkin et al. 2006 (CR002434)]
 
−
|2001-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#VAD_doxil|DVd]]
 
−
|style="background-color:#eeee01"|Non-inferior ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5394869/ Straka et al. 2016 (DSMM-II)]
 
−
|2001-2006
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#No_induction_99|No]] induction
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for patients greater than or equal to 18 years and fulfilling a diagnosis of stage II or III MM according to the [[Multiple_myeloma#Durie-Salmon_Staging_System_-_1975|Durie and Salmon criteria]]. Note that Straka et al. 2016 does not describe dosing; placed here given that it is contemporary to these trials.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*IFM 99-02: [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|MEL140 & MEL200 tandem auto HSCT]], after 3 to 4 cycles
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 0.4/9/40 (CI doxorubicin & vincristine, dex 8 days/cycle) {{#subobject:81da72|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/full/10.1002/cncr.21666 Friedenberg et al. 2006 (ECOG E1A95)]
 
−
|1997-2000
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VAD_.26_Valspodar_77|VAD & Valspodar]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 15 to 18
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 0.4/9/40 (bolus doxorubicin & vincristine, dex 12 days/cycle in cycles 1-3) {{#subobject:20136a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1093/annonc/mdg287 Dimopoulos et al. 2003]
 
−
|1999-2001
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_induction#VAD.28Pegylated_liposomal_doxorubicin_substituted.29|VAD doxil]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for all patients with previously untreated multiple myeloma who were considered candidates for systemic treatment.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV over 30 minutes once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 3: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycles 2 & 4: 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Fluconazole (Diflucan)]] 200 mg PO once per day
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] 960 mg (paper did not specify which component was 960 mg) PO twice per day for "prophylaxis"
 
−
'''28-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 0.4/9/40 (CI doxorubicin & vincristine, dex 12 days/cycle) {{#subobject:3548e2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.5807 Barlogie et al. 2006 (SWOG S9321)]
 
−
|1993-NR
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
====Supportive therapy====
 
−
*[[Cimetidine (Tagamet)]] prophylaxis (dose not specified)
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] prophylaxis (dose not specified)
 
−
'''35-day cycles (see below)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SD or better: Randomized after 4 cycles to [[#VBMCP|VBMCP]] versus [[#Melphalan_.26_TBI.2C_then_auto_HSCT|melphalan & TBI, then auto HSCT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, 0.4/9/40 (Bolus doxorubicin, CI vincristine, dex 12 days per odd cycle) {{#subobject:2b093b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.1999.01279.x Segeren et al. 1999]
 
−
|1995-1998
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV over 30 minutes once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 4
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Odd cycles: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
====Supportive therapy====
 
−
*[[Fluconazole (Diflucan)]] 200 mg PO once per day
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] 960 mg (paper did not specify which component was 960 mg) PO twice per day for "prophylaxis"
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #8, 0.4/9/40 (CI doxorubicin & vincristine, dex 4 days per odd cycle) {{#subobject:b7400b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(89)91549-3 Samson et al. 1989]
 
−
|1984-1988
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.10.2509 Cavo et al. 2007 (Bologna 96)]
 
−
|1996-2001
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: In Samson et al. 1989, the odd cycles were 21 days in length. In Bologna 96, this regimen was intended for patients with a confirmed diagnosis of symptomatic or progressive MM, an upper age limit of 60 years, and previously untreated.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 3: 40 mg PO once per day on days 1 to 4
 
−
**Cycles 2 & 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
'''28-day cycle for 4 cycles (Bologna 96) or indefinitely (Samson et al. 1989)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Bologna 96, responders: [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|Single autologous hematopoietic cell transplant]] versus [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem autologous hematopoietic cell transplant]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #9, 2/50/40 {{#subobject:8d0e51|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.haematologica.org/content/89/9/1124.long Corso et al. 2004]
 
−
|1996-2002
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4, 14 to 17
 
−
'''2 cycles (length not specified)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Stem_cell_mobilization#DCEP_.26_G-CSF|DCEP & G-CSF with stem cell mobilization]], then [[#Melphalan.2C_then_auto_HSCT|high dose melphalan with auto HSCT]]
 
−
</div></div>
 
−
===References===
 
−
# Samson D, Gaminara E, Newland A, Van de Pette J, Kearney J, McCarthy D, Joyner M, Aston L, Mitchell T, Hamon M, Barrett AJ, Evans M. Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet. 1989 Oct 14;2(8668):882-5. [https://doi.org/10.1016/S0140-6736(89)91549-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2571813 PubMed]
 
−
# Segeren CM, Sonneveld P, van der Holt B, Baars JW, Biesma DH, Cornellissen JJ, Croockewit AJ, Dekker AW, Fibbe WE, Löwenberg B, van Marwijk Kooy M, van Oers MH, Richel DJ, Schouten HC, Vellenga E, Verhoef GE, Wijermans PW, Wittebol S, Lokhorst HM. Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma. Br J Haematol. 1999 Apr;105(1):127-30. [https://doi.org/10.1111/j.1365-2141.1999.01279.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10233375 PubMed]
 
−
# Dimopoulos MA, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P, Mitsouli C, Papanastasiou C, Margaritis D, Tokmaktsis A, Katodritou I, Kokkini G, Terpos E, Vyniou N, Tzilianos M, Chatzivassili A, Kyrtsonis MC, Panayiotidis P, Maniatis A; Greek Myeloma Study Group. Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Ann Oncol. 2003 Jul;14(7):1039-44. [https://doi.org/10.1093/annonc/mdg287 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12853344 PubMed]
 
−
# Corso A, Barbarano L, Zappasodi P, Cairoli R, Alessandrino EP, Mangiacavalli S, Ferrari D, Fava S, Fiumanò M, Frigerio G, Isa L, Luraschi A, Klersy C, De Paoli A, Vergani C, Banfi L, Perego D, Ucci G, Pinotti G, Savarè M, Uziel L, Vismara A, Morra E, Lazzarino M. The VAD-DCEP sequence is an effective pre-transplant therapy in untreated multiple myeloma. Haematologica. 2004 Sep;89(9):1124-7. [http://www.haematologica.org/content/89/9/1124.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15377474 PubMed]
 
−
# '''WOS MM1:''' Cook G, Clark RE, Morris TC, Robertson M, Lucie NP, Anderson S, Paul J, Franklin IM. A randomized study (WOS MM1) comparing the oral regime Z-Dex (idarubicin and dexamethasone) with vincristine, adriamycin and dexamethasone as induction therapy for newly diagnosed patients with multiple myeloma. Br J Haematol. 2004 Sep;126(6):792-8. [https://doi.org/full/10.1111/j.1365-2141.2004.05127.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15352982 PubMed] NCT00006232
 
−
# '''IFM99-03:''' Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. Epub 2006 Jan 5. [http://www.bloodjournal.org/content/107/9/3474 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16397129 PubMed]
 
−
## '''Pooled update:''' Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008 Nov 1;112(9):3914-5. [http://www.bloodjournal.org/content/112/9/3914.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18948589 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. [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]
 
−
# '''ECOG E1A95:''' Friedenberg WR, Rue M, Blood EA, Dalton WS, Shustik C, Larson RA, Sonneveld P, Greipp PR. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer. 2006 Feb 15;106(4):830-8. [https://doi.org/full/10.1002/cncr.21666 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16419071 PubMed] NCT00002878
 
−
# '''CR002434:''' Rifkin RM, Gregory SA, Mohrbacher A, Hussein MA. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a phase III multicenter randomized trial. Cancer. 2006 Feb 15;106(4):848-58. [https://doi.org/10.1002/cncr.21662 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16404741 PubMed] NCT00344422
 
−
# '''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. [http://www.bloodjournal.org/content/108/10/3289.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16873668 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. [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]
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17485707 PubMed] NCT00378222
 
−
## '''Subgroup analysis:''' Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, de Vivo A, Testoni N, Nicci C, Terragna C, Grafone T, Perrone G, Ceccolini M, Tura S, Baccarani M; Bologna 2002 study. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005 Jul 1;106(1):35-9. Epub 2005 Mar 10. [http://www.bloodjournal.org/content/106/1/35 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15761019 PubMed]
 
−
# '''SWOG S9321:''' Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, McCoy J, Moore DF Jr, Dakhil SR, Lanier KS, Chapman RA, Cromer JN, Salmon SE, Durie B, Crowley JC. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006 Feb 20;24(6):929-36. Epub 2006 Jan 23. Erratum in: J Clin Oncol. 2006 Jun 10;24(17):2687. Moore, Dennis F Jr [added]. [https://doi.org/10.1200/jco.2005.04.5807 link to original article] '''refers to protocol in [https://doi.org/10.1056/NEJM198405243102104 Barlogie et al. 1984]''' [https://pubmed.ncbi.nlm.nih.gov/16432076 PubMed] NCT00002548
 
−
## '''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]
 
−
<!-- 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. [http://www.bloodjournal.org/content/115/6/1113 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19880501 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. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905 PubMed]
 
−
<!-- 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. [https://doi.org/10.1200/jco.2009.27.9158 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20823406 PubMed] NCT00200681
 
−
# '''HOVON-65/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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22802322 PubMed] NTR213
 
−
## '''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. [http://www.bloodjournal.org/content/119/4/940.long 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]
 
−
# '''DSMM-II:''' Straka C, Liebisch P, Salwender H, Hennemann B, Metzner B, Knop S, Adler-Reichel S, Gerecke C, Wandt H, Bentz M, Bruemmendorf TH, Hentrich M, Pfreundschuh M, Wolf HH, Sezer O, Bargou R, Jung W, Trümper L, Hertenstein B, Heidemann E, Bernhard H, Lang N, Frickhofen N, Hebart H, Schmidmaier R, Sandermann A, Dechow T, Reichle A, Schnabel B, Schäfer-Eckart K, Langer C, Gramatzki M, Hinke A, Emmerich B, Einsele H. Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial. Haematologica. 2016 Nov;101(11):1398-1406. Epub 2016 Aug 4. [https://doi.org/10.3324/haematol.2016.151860 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5394869/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27662018/ PubMed] NCT02288741
 
−
==VAMP {{#subobject:057275|Regimen=1}}==
 
−
VAMP: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethyl'''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8c5f22|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/S0140-6736(89)91548-1 Gore et al. 1989]
 
−
|1985-1988
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1046/j.1365-2141.1997.d01-2122.x Raje et al. 1997]
 
−
|1985-1994
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/92/9/3131.long Fermand et al. 1998]
 
−
|1990-1995
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#VMCP|VMCP]]
 
−
| style="background-color:#91cf60" |Seems to have superior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.03.0551 Fermand et al. 2005]
 
−
|1991-1998
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#VMCP|VMCP]]
 
−
| style="background-color:#d9ef8b" |Might have superior EFS
 
−
|-
 
−
|}
 
−
''Note: this is to be distinguished from the VAMP protocols used in AML and Hodgkin lymphoma.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Methylprednisolone (Solumedrol)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Raje et al. 1997: [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|HDT with autograft (details not specified in abstract)]]
 
−
*Fermand et al. 1998: [[#Lomustine.2C_Melphalan.2C_TBI.2C_then_auto_HSCT_88|Lomustine, melphalan, TBI with auto HSCT]]
 
−
*Fermand et al. 2005: [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|MEL200 with auto HSCT]] or [[#Melphalan_.26_Busulfan.2C_then_auto_HSCT_88|melphalan & busulfan with auto HSCT]]
 
−
</div></div>
 
−
===References===
 
−
# Gore ME, Selby PJ, Viner C, Clark PI, Meldrum M, Millar B, Bell J, Maitland JA, Milan S, Judson IR, Tillyer C, Malpas JS, McElwain TJ. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet. 1989 Oct 14;2(8668):879-82. [https://doi.org/10.1016/S0140-6736(89)91548-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2571812 PubMed]
 
−
# Raje N, Powles R, Kulkarni S, Milan S, Middleton G, Singhal S, Mehta J, Millar B, Viner C, Raymond J, Treleaven J, Cunningham D, Gore M. A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma. Br J Haematol. 1997 Apr;97(1):153-60. [https://doi.org/10.1046/j.1365-2141.1997.d01-2122.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9136958 PubMed]
 
−
# Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, Macro M, Pertuiset E, Dreyfus F, Mariette X, Boccacio C, Brouet JC. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998 Nov 1;92(9):3131-6. [http://www.bloodjournal.org/content/92/9/3131.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9787148 PubMed]
 
−
# Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, Arnulf B, Royer B, Mariette X, Pertuiset E, Belanger C, Janvier M, Chevret S, Brouet JC, Ravaud P; Group Myelome-Autogreffe. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005 Dec 20;23(36):9227-33. Epub 2005 Nov 7. [https://doi.org/10.1200/JCO.2005.03.0551 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16275936 PubMed]
 
−
==VBMC {{#subobject:5e5c89|Regimen=1}}==
 
−
VBMC: '''<u>V</u>'''incristine, '''<u>B</u>'''iCNU (Carmustine), '''<u>M</u>'''elphalan, '''<u>C</u>'''yclophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:486966|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)]
 
−
|1993-2000
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Melphalan_.26_Methylprednisolone.2C_then_auto_HSCT|Melphalan & Methylprednisolone, then auto HSCT]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Interferon_alfa_monotherapy|Interferon alfa]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. [https://doi.org/10.1056/NEJMoa022340 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12736280 PubMed]
 
−
==VBMCP {{#subobject:7bd579|Regimen=1}}==
 
−
VBMCP: '''<u>V</u>'''incristine, '''<u>B</u>'''iCNU (Carmustine), '''<u>M</u>'''elphalan, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
<br>VBCMP: '''<u>V</u>'''incristine, '''<u>B</u>'''iCNU (Carmustine), '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ff3db2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/full/10.1002/%28SICI)1097-0142%2819970415%2979%3A8%3C1561%3A%3AAID-CNCR18%3E3.0.CO%3B2-W Oken et al. 1997 (ECOG E2479)]
 
−
|1979-1983
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#Melphalan_.26_Prednisone_.28MP.29|MP]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|rowspan=2|[https://doi.org/full/10.1002/%28SICI)1097-0142%2819990915%2986%3A6%3C957%3A%3AAID-CNCR10%3E3.0.CO%3B2-8 Oken et al. 1999 (ECOG E9486)]
 
−
|rowspan=2|1988-1992
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#VBMCP.2FHiCy_99|VBMCP/HiCy]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#VBMCP.2FInterferon_88|VBMCP/IFN]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.5807 Barlogie et al. 2006 (SWOG S9321)]
 
−
|1993-NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Melphalan_.26_TBI.2C_then_auto_HSCT|Melphalan & TBI, then auto HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066392/ Kyle et al. 2009 (ECOG E5A93)]
 
−
|1994-2002
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VBMCP.2FHiCy_.26_Inteferon_99|VBMCP/HiCy & IFN]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Hansen OP, Clausen NA, Drivsholm A, Laursen B. Phase III study of intermittent 5-drug regimen (VBCMP) versus intermittent 3-drug regimen (VMP) versus intermittent melphalan and prednisone (MP) in myelomatosis. Scand J Haematol. 1985 Nov;35(5):518-24. [https://doi.org/10.1111/j.1600-0609.1985.tb02822.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/3911373 PubMed]
 
−
# '''ECOG E2479:''' Oken MM, Harrington DP, Abramson N, Kyle RA, Knospe W, Glick JH. Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer. 1997 Apr 15;79(8):1561-7. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819970415%2979%3A8%3C1561%3A%3AAID-CNCR18%3E3.0.CO%3B2-W link to original article] [https://pubmed.ncbi.nlm.nih.gov/9118039 PubMed]
 
−
# '''ECOG E9486:''' Oken MM, Leong T, Lenhard RE Jr, Greipp PR, Kay NE, Van Ness B, Keimowitz RM, Kyle RA. The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma: phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486. Cancer. 1999 Sep 15;86(6):957-68. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819990915%2986%3A6%3C957%3A%3AAID-CNCR10%3E3.0.CO%3B2-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10491521 PubMed]
 
−
# '''SWOG S9321:''' Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, McCoy J, Moore DF Jr, Dakhil SR, Lanier KS, Chapman RA, Cromer JN, Salmon SE, Durie B, Crowley JC. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006 Feb 20;24(6):929-36. Epub 2006 Jan 23. Erratum in: J Clin Oncol. 2006 Jun 10;24(17):2687. Moore, Dennis F Jr [added]. [https://doi.org/10.1200/jco.2005.04.5807 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16432076 PubMed] NCT00002548
 
−
## '''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]
 
−
# '''ECOG E5A93:''' Kyle RA, Jacobus S, Friedenberg WR, Slabber CF, Rajkumar SV, Greipp PR. The treatment of multiple myeloma using vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alternating with high-dose cyclophosphamide and alpha(2)beta interferon versus VBMCP: results of a phase III Eastern Cooperative Oncology Group Study E5A93. Cancer. 2009 May 15;115(10):2155-64. [https://doi.org/full/10.1002/cncr.24221 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066392/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19248045 PubMed] NCT00002556
 
−
==VBMCP/VBAD {{#subobject:ad5cbe|Regimen=1}}==
 
−
VBMCP/VBAD: '''<u>V</u>'''incristine, '''<u>B</u>'''iCNU (Carmustine), '''<u>M</u>'''elphalan, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone alternating with '''<u>V</u>'''incristine, '''<u>B</u>'''iCNU (Carmustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:2326f0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/106/12/3755 Bladé et al. 2005]
 
−
|1994-1999
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|[http://www.bloodjournal.org/content/112/9/3591.long Rosiñol et al. 2008 (PETHEMA MM 2000)]
 
−
|1999-2004
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, VBMCP portion====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
====Glucocorticoid therapy, VBMCP portion====
 
−
*[[Prednisone (Sterapred)]]
 
−
====Chemotherapy, VBAD portion====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
====Glucocorticoid therapy, VBAD portion====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Bladé et al. 2005, with response after 4 cycles: [[#VBMCP.2FVBAD|VBMCP/VBAD]] x 8 (12 cycles total) versus HDT with [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|MEL200 with auto HSCT]] or [[#Melphalan_.26_TBI.2C_then_auto_HSCT|MEL140 & TBI with auto HSCT]]
 
−
*PETHEMA MM 2000: Bu/Mel with tandem auto HSCT versus Bu/Mel with auto HSCT, then RIC allo HSCT
 
−
</div></div>
 
−
===References===
 
−
# 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. [http://www.bloodjournal.org/content/106/12/3755 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16105975 PubMed]
 
−
# '''PETHEMA MM 2000:''' Rosiñol L, Pérez-Simón JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ, González JD, Díaz-Mediavilla J, Hernández B, García-Frade J, Carrera D, León A, Hernández M, Abellán PF, Bergua JM, San Miguel J, Bladé J; PETHEMA; GEM. A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood. 2008 Nov 1;112(9):3591-3. Epub 2008 Jul 8. [http://www.bloodjournal.org/content/112/9/3591.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/18612103 PubMed] NCT00560053
 
−
==VMCP {{#subobject:fab3f3|Regimen=1}}==
 
−
VMCP: '''<u>V</u>'''incristine, '''<u>M</u>'''elphalan, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
<br>VCMP: '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f90413|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1002/1097-0142(197712)40:6%3C2765::AID-CNCR2820400602%3E3.0.CO;2-X Alexanian et al. 1977 (SWOG S7305)]
 
−
|1973-1974
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|Alkylator-prednisone combinations
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.03.0551 Fermand et al. 2005]
 
−
|1991-1998
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VAMP_88|VAMP, then auto HSCT]]
 
−
|style="background-color:#fee08b"|Might have inferior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 80 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
'''1-month cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S7305:''' Alexanian R, Salmon S, Bonnet J, Gehan E, Haut A, Weick J. Combination therapy for multiple myeloma. Cancer. 1977 Dec;40(6):2765-71. [https://doi.org/10.1002/1097-0142(197712)40:6%3C2765::AID-CNCR2820400602%3E3.0.CO;2-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/589554 PubMed]
 
−
# Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, Arnulf B, Royer B, Mariette X, Pertuiset E, Belanger C, Janvier M, Chevret S, Brouet JC, Ravaud P; Group Myelome-Autogreffe. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005 Dec 20;23(36):9227-33. Epub 2005 Nov 7. [https://doi.org/10.1200/JCO.2005.03.0551 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16275936 PubMed]
 
−
==VMCP/VBAP {{#subobject:fdb3f3|Regimen=1}}==
 
−
VMCP/VBAP: '''<u>V</u>'''incristine, '''<u>M</u>'''elphalan, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone alternating with '''<u>V</u>'''incristine, '''<u>B</u>'''iCNU (Carmustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:f90513|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.1986.4.8.1227 Durie et al. 1986 (SWOG S7927/S7928)]
 
−
|1979-1982
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#CVP|VCP]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1990.8.9.1575 Salmon et al. 1990 (SWOG S8229/S8230)]
 
−
|1982-1987
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199607113350204 Attal et al. 1996 (IFM90)]
 
−
|1990-1993
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, VMCP portion====
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
*[[Melphalan (Alkeran)]] 5 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 110 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
====Glucocorticoid therapy, VMCP portion====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
'''21-day cycle for 2 to 3 cycles, alternating with VBAP'''
 
−
====Chemotherapy, VBAP portion====
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
*[[Carmustine (BCNU)]] 30 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy, VBAP portion====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 4
 
−
'''21-day cycle for 2 to 3 cycles, alternating with VMCP'''
 
−
'''VMCP and VBAP are given in an alternating fashion for a total of 4 to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*IFM90: Patients with a WHO performance status less than 3, creatinine less than 1.7 mg/dL (150 µmol/L), and bone marrow (collected after cycle 4) with greater than 200 million nucleated cells/kg: [[#Melphalan_.26_TBI.2C_then_auto_HSCT|melphalan, total body irradiation (TBI), and autologous transplant]] versus [[#VMCP.2FVBAP|VMCP/VBAP]] x 18 total cycles
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S7927/S7928:''' Durie BG, Dixon DO, Carter S, Stephens R, Rivkin S, Bonnet J, Salmon SE, Dabich L, Files JC, Costanzi JJ. Improved survival duration with combination chemotherapy induction for multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1986 Aug;4(8):1227-37. [https://doi.org/10.1200/JCO.1986.4.8.1227 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3525768 PubMed]
 
−
# '''SWOG S8229/S8230:''' Salmon SE, Tesh D, Crowley J, Saeed S, Finley P, Milder MS, Hutchins LF, Coltman CA Jr, Bonnet JD, Cheson B, Knost JA, Samhouri A, Beckord J, Stock-Novack D. Chemotherapy is superior to sequential hemibody irradiation for remission consolidation in multiple myeloma: a Southwest Oncology Group study. J Clin Oncol. 1990 Sep;8(9):1575-84. [https://doi.org/10.1200/JCO.1990.8.9.1575 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2131793 PubMed]
 
−
# '''IFM90:''' Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R; Intergroupe Français du Myélome. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996 Jul 11;335(2):91-7. [https://doi.org/10.1056/NEJM199607113350204 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8649495 PubMed]
 
−
==VMCP/VCAP {{#subobject:d7d0bd|Regimen=1}}==
 
−
VMCP/VCAP: '''<u>V</u>'''incristine, '''<u>M</u>'''elphalan, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone alternating with '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:fb80f1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.1983.1.8.453 Salmon et al. 1983 (SWOG S7704)]
 
−
|1977-1979
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#Melphalan_.26_Prednisone_.28MP.29|MP]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, VMCP portion====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
====Glucocorticoid therapy, VMCP portion====
 
−
*[[Prednisone (Sterapred)]]
 
−
====Chemotherapy, VCAP portion====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
====Glucocorticoid therapy, VCAP portion====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S7704:''' Salmon SE, Haut A, Bonnet JD, Amare M, Weick JK, Durie BG, Dixon DO. Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1983 Aug;1(8):453-61. [https://doi.org/10.1200/JCO.1983.1.8.453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6366141 PubMed]
 
−
=Consolidation after first-line therapy=
 
−
==Melphalan monotherapy {{#subobject:79b2d2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0ee0ca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(83)90739-0 McElwain & Powles 1983]
 
−
|NR
 
−
|style="background-color:#ffffbe"|Pilot Study
 
−
|-
 
−
|[http://www.bloodjournal.org/content/101/6/2144.long Segeren et al. 2003 (HOVON 24)]
 
−
|1995-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note that this is highly obsolete but included for historical interest. Stem cell rescue was NOT used.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*HOVON 24: [[#VAD|VAD]] x 3 to 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 70 to 140 mg/m<sup>2</sup> IV for one or more doses
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*HOVON 24: Cy/TBI with auto HSCT, then [[#Interferon_alfa_monotherapy|interferon]] maintenance versus [[#Interferon_alfa_monotherapy|interferon]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983 Oct 8;2(8354):822-4. [https://doi.org/10.1016/S0140-6736(83)90739-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6137651 PubMed]
 
−
# '''HOVON 24:''' Segeren CM, Sonneveld P, van der Holt B, Vellenga E, Croockewit AJ, Verhoef GE, Cornelissen JJ, Schaafsma MR, van Oers MH, Wijermans PW, Fibbe WE, Wittebol S, Schouten HC, van Marwijk Kooy M, Biesma DH, Baars JW, Slater R, Steijaert MM, Buijt I, Lokhorst HM; HOVON. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study. Blood. 2003 Mar 15;101(6):2144-51. Epub 2002 Nov 27. [http://www.bloodjournal.org/content/101/6/2144.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12456509 PubMed]
 
−
## '''Update:''' Sonneveld P, van der Holt B, Segeren CM, Vellenga E, Croockewit AJ, Verhoe GE, Cornelissen JJ, Schaafsma MR, van Oers MH, Wijermans PW, Westveer PH, Lokhorst HM; HOVON. Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial. Haematologica. 2007 Jul;92(7):928-35. [http://www.haematologica.org/content/92/7/928.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/17606443 PubMed]
 
−
==Melphalan, then auto HSCT, then Melphalan & Busulfan, then auto HSCT {{#subobject:71ae0c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:655c75|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2006.10.2509 Cavo et al. 2007 (Bologna 96)]
 
−
|1996-2001
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#Melphalan.2C_then_auto_HSCT|Melphalan, then auto HSCT]]
 
−
|style="background-color:#1a9850"|Superior EFS<br>Median EFS: 35 vs 23 mo
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, first transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2
 
−
'''Stem cells re-infused on day 0'''
 
−
====Chemotherapy, second transplant====
 
−
*[[Melphalan (Alkeran)]] 120 mg/m<sup>2</sup> IV once on day -4
 
−
*[[Busulfan (Myleran)]] 4 mg/kg PO from day -5 to -3
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17485707 PubMed]
 
−
==MEL200, then auto HSCT, then MEL220 & Dexamethasone, then auto HSCT {{#subobject:9f3119|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:5a4ee1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/1/397.long Moreau et al. 2005 (IFM 99-04)]
 
−
|2000-2004
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Melphalan_monotherapy_99|MEL200]], then [[#Melphalan.2C_Dexamethasone.2C_B-E8_77|MEL220 + Dex + B-E8]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
''Note: This regimen was meant for patients who did not have an HLA-identical sibling donor.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VAD|VAD]] induction x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, first transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2
 
−
'''Stem cells re-infused on day 0'''
 
−
====Chemotherapy, second transplant====
 
−
*[[Melphalan (Alkeran)]] 220 mg/m<sup>2</sup> IV once on day -2
 
−
====Glucocorticoid therapy, second transplant====
 
−
*[[Dexamethasone (Decadron)]] 40 mg (route not specified) over 4 days (days not specified)
 
−
'''Stem cells re-infused on day 0'''
 
−
''No further treatment.''
 
−
</div></div>
 
−
===References===
 
−
# '''IFM 99-04:''' Moreau P, Hullin C, Garban F, Yakoub-Agha I, Benboubker L, Attal M, Marit G, Fuzibet JG, Doyen C, Voillat L, Berthou C, Ketterer N, Casassus P, Monconduit M, Michallet M, Najman A, Sotto JJ, Bataille R, Harousseau JL; Intergroupe Francophone du Myélome. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol. Blood. 2006 Jan 1;107(1):397-403. Epub 2005 Sep 13. [http://www.bloodjournal.org/content/107/1/397.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16144800 PubMed]
 
−
## '''Pooled update:''' Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. Epub 2006 Jan 5. [http://www.bloodjournal.org/content/107/9/3474 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16397129 PubMed]
 
−
## '''Pooled update:''' Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008 Nov 1;112(9):3914-5. [http://www.bloodjournal.org/content/112/9/3914.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18948589 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. [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]
 
−
==Melphalan, then auto HSCT, then Melphalan & TBI, then auto HSCT {{#subobject:9ac748|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #1, lower radiation {{#subobject:4e0ef9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa032290 Attal et al. 2003 (IFM94)]
 
−
|1994-1997
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#Melphalan_.26_TBI.2C_then_auto_HSCT|MEL140-TBI & auto HSCT]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS84: 42% vs 21%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VAD|VAD]] x 3 to 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, first transplant====
 
−
*[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once per day on days -3 & -2
 
−
'''Stem cells re-infused on day 0'''
 
−
====Chemotherapy, second transplant====
 
−
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -4
 
−
====Radiotherapy====
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] in 2 Gy fractions once per day x 4 = total dose of 8 Gy, without lung shielding
 
−
'''Stem cells re-infused on day 0'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Interferon_alfa_monotherapy|Interferon alfa]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #2, higher radiation {{#subobject:4e0fj9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/89/3/789.long Barlogie et al. 1997 (Total Therapy 1)]
 
−
|1990-1994
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
''Note: this regimen was intended for patients not achieving at least PR after the first transplant.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, first transplant====
 
−
*[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once per day on days -3 & -2
 
−
'''Stem cells re-infused on day 0'''
 
−
====Chemotherapy, second transplant====
 
−
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -4
 
−
====Radiotherapy====
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]]: 850 to 1020 cGy in 5 to 6 fractions delivered on days -3 to -1
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===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. [http://www.bloodjournal.org/content/89/3/789.long 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. [http://www.bloodjournal.org/content/93/1/55.long link to original article] '''contains dosing details in manuscript''' [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. [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]
 
−
# '''IFM94:''' Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R; InterGroupe Francophone du Myélome. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003 Dec 25;349(26):2495-502. Erratum in: N Engl J Med. 2004 Jun17;350(25):2628. [https://doi.org/10.1056/NEJMoa032290 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14695409 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. [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]
 
−
==Melphalan, then auto HSCT, then Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:f4bb75|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:bf9741|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/9/3474 Garban et al. 2006 (IFM99-03)]
 
−
|2000-2004
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
''Note: This regimen was meant for patients who had an HLA-identical sibling donor.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VAD|VAD]] induction x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, auto HSCT====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2
 
−
'''Stem cells re-infused on day 0, followed in two months by:'''
 
−
====Chemotherapy, allo HSCT====
 
−
{{#lst:Allogeneic HSCT|e2d51e}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# '''IFM99-03:''' Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. Epub 2006 Jan 5. [http://www.bloodjournal.org/content/107/9/3474 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16397129 PubMed]
 
−
## '''Pooled update:''' Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008 Nov 1;112(9):3914-5. [http://www.bloodjournal.org/content/112/9/3914.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18948589 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. [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]
 
−
==Melphalan, then auto HSCT, then TBI, then allo HSCT {{#subobject:f4ee75|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:8f0993|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa065464 Bruno et al. 2007]
 
−
|1998-2004
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
''Note: This regimen was meant for patients who had an HLA-identical sibling donor.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VAD|VAD]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, auto HSCT====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV once on day -2
 
−
'''Stem cells re-infused on day 0, followed by:'''
 
−
====Radiotherapy, allo HSCT====
 
−
*[[External beam radiotherapy|TBI]] 2 Gy
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# 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] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/17360989 PubMed] NCT00415987
 
−
==Melphalan & Methylprednisolone, then auto HSCT {{#subobject:7305c0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:06aa41|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)]
 
−
|1993-2000
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#VBMC|VBMC]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: 54.1 vs 42.3 mo
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VAMP|VAMP]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Methylprednisolone (Solumedrol)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Interferon_alfa_monotherapy|Interferon alfa]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. [https://doi.org/10.1056/NEJMoa022340 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12736280 PubMed]
 
−
==Melphalan & TBI, then auto HSCT {{#subobject:bffa53|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, MEL140 & TBI 8 Gy {{#subobject:f1d04f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJM199607113350204 Attal et al. 1996 (IFM90)]
 
−
|1990-1993
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#VMCP.2FVBAP_88|VMCP/VBAP]] x 18
 
−
|style="background-color:#91cf60"|Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.5807 Barlogie et al. 2006 (SWOG S9321)]
 
−
|1993-NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#VBMCP|VBMCP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa032290 Attal et al. 2003 (IFM94)]
 
−
|1994-1997
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Melphalan.2C_then_auto HSCT.2C_then_Melphalan_.26_TBI.2C_then_auto HSCT|Melphalan, then auto HSCT, then Melphalan & TBI, then auto HSCT]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/99/3/731.long Moreau et al. 2002 (IFM 9502)]
 
−
|1995-1999
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|High-dose melphalan & autologous transplant]]
 
−
|style="background-color:#fee08b"|Might have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*IFM90: [[#VMCP.2FVBAP|VMCP alternating with VBAP]] x 4 to 6 cycles
 
−
*IFM 9502 and SWOG S9321: [[#VAD|VAD]] x 3
 
−
*IFM 94: [[#VAD|VAD]] x 3 to 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV (day not specified)
 
−
====Radiotherapy====
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] in 2 Gy fractions once per day x 4 = total dose of 8 Gy, without lung shielding
 
−
'''One course; relative date of stem cell re-infusion not specified'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Interferon_alfa_monotherapy|Interferon alfa]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, MEL140 & TBI 12 Gy {{#subobject:f1d04f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/106/12/3755 Bladé et al. 2005]
 
−
|1994-1999
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ooc)
 
−
|1. [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|MEL200 with auto HSCT]]<br>2. [[#VBMCP.2FVBAD|VBMCP/VBAD]]
 
−
|style="background-color:#ffffbf"|Did not meet endpoints of PFS/OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>It is not clear from the manuscript what the primary endpoint was. While this regimen had inferior CR, there was no difference in PFS or OS.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VBMCP.2FVBAD|VBMCP/VBAD]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2
 
−
====Radiotherapy====
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] in 3 Gy fractions once per day on days -6 to -3 = total dose of 12 Gy
 
−
'''Re-infusion of stem cells on day 0'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Interferon_alfa_.26_Dexamethasone|IFN & Dex]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''IFM90:''' Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R; Intergroupe Français du Myélome. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996 Jul 11;335(2):91-7. [https://doi.org/10.1056/NEJM199607113350204 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8649495 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. [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 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. [http://www.bloodjournal.org/content/99/3/731.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11806971 PubMed]
 
−
# '''IFM94:''' Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R; InterGroupe Francophone du Myélome. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003 Dec 25;349(26):2495-502. Erratum in: N Engl J Med. 2004 Jun17;350(25):2628. [https://doi.org/10.1056/NEJMoa032290 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14695409 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. [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]
 
−
# 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. [http://www.bloodjournal.org/content/106/12/3755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16105975 PubMed]
 
−
# '''SWOG S9321:''' Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, McCoy J, Moore DF Jr, Dakhil SR, Lanier KS, Chapman RA, Cromer JN, Salmon SE, Durie B, Crowley JC. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006 Feb 20;24(6):929-36. Epub 2006 Jan 23. Erratum in: J Clin Oncol. 2006 Jun 10;24(17):2687. Moore, Dennis F Jr [added]. [https://doi.org/10.1200/jco.2005.04.5807 link to original article] '''refers to protocol in [https://doi.org/10.1056/NEJM198405243102104 Barlogie et al. 1984]''' [https://pubmed.ncbi.nlm.nih.gov/16432076 PubMed] NCT00002548
 
−
## '''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]
 
−
=Maintenance after first-line therapy=
 
−
==Dexamethasone monotherapy {{#subobject:5db0eb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1 year {{#subobject:9b6dc4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1002/ajh.23274 Maiolino et al. 2012 (GBRAM0001)]
 
−
|2003-2008
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_.26_Dexamethasone_.28TD.29_2|Thal-Dex]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|High-dose melphalan with autologous hematopoietic stem cell transplant]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycle for 13 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:c59616|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(10)61424-9 Cavo et al. 2010 (GIMEMA MM-BO2005)]
 
−
|2006-2008
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_.26_Dexamethasone_.28TD.29|TD]] versus [[Multiple_myeloma,_consolidation_and_maintenance#VTD|VTD]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Acyclovir (Zovirax)]] prophylaxis recommended
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===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 Italian Myeloma Network. 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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21146205 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 (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network. 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. [http://www.bloodjournal.org/content/120/1/9.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22498745 PubMed]
 
−
<!-- 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://doi.org/10.1002/ajh.23274 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22730113 PubMed] NCT01296503
 
−
==Interferon alfa monotherapy {{#subobject:d82e88|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c4ce8d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/115/6/1113 Lokhorst et al. 2009 (HOVON-50)]
 
−
|2001-2005
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Complex_multipart_regimens#HOVON-50|See link]]
 
−
|style="background-color:#d73027"|[[Complex_multipart_regimens#HOVON-50|See link]]
 
−
|-
 
−
|}
 
−
''Note: these trials do not specify an exact type of interferon alfa.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*HOVON-50: [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[:Category:Interferons|Interferon alfa]]
 
−
</div></div>
 
−
===References===
 
−
# '''IFM90:''' Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R; Intergroupe Français du Myélome. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996 Jul 11;335(2):91-7. [https://doi.org/10.1056/NEJM199607113350204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8649495 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. [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]
 
−
<!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 7, 2008. -->
 
−
# '''Meta-analysis:''' Fritz E, Ludwig H. Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients. Ann Oncol. 2000 Nov;11(11):1427-36. [https://doi.org/10.1023/a:1026548226770 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11142483 PubMed]
 
−
<!-- 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. [http://www.bloodjournal.org/content/115/6/1113 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19880501 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. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905 PubMed]
 
−
==Interferon alfa-2a monotherapy {{#subobject:d82y44|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c4326d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2a (Roferon-A)]]
 
−
</div></div>
 
−
===References===
 
−
# '''MRC Myeloma VII:''' Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. [https://doi.org/10.1056/NEJMoa022340 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12736280 PubMed] NCT00002599
 
−
==Interferon alfa-2b monotherapy {{#subobject:d77t88|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c4ca9p|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJM199005173222005 Mandelli et al. 1990]
 
−
|1985-1988
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1995.13.9.2354 Browman et al. 1995]
 
−
|1987-1992
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdi125 Schaar et al. 2005 (HOVON-16)]
 
−
|1991-1997
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Multiple_myeloma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2008-07-169565 Ludwig et al. 2008 (01-002-0601)]
 
−
|2001-2007
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Interferon_alfa-2b_.26_Thalidomide|Interferon alfa-2b & Thalidomide]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|rowspan=2|[http://www.bloodjournal.org/content/120/8/1589.long Rosiñol et al. 2012 (GEM05/MENOS65)]
 
−
|rowspan=2|2006-2009
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_monotherapy|Thalidomide]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[Multiple_myeloma,_consolidation_and_maintenance#VT|VT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for GEM05/MENOS65 is based on the 2017 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Mandelli et al. 1990: [[#Melphalan_.26_Prednisone_.28MP.29|MP]] x 12 mo or [[#VMCP.2FVBAP|VMCP/VBAP]] x 12 mo
 
−
*HOVON-16: [[#Melphalan_.26_Prednisone_.28MP.29|MP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2b (Intron-A)]]
 
−
</div></div>
 
−
===References===
 
−
# Mandelli F, Avvisati G, Amadori S, Boccadoro M, Gernone A, Lauta VM, Marmont F, Petrucci MT, Tribalto M, Vegna ML, Dammacco F, Pileri A. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med. 1990 May 17;322(20):1430-4. [https://doi.org/10.1056/NEJM199005173222005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2184356 PubMed]
 
−
# Browman GP, Bergsagel D, Sicheri D, O'Reilly S, Wilson KS, Rubin S, Belch A, Shustik C, Barr R, Walker I, James K, Zee B, Johnston D; National Cancer Institute of Canada Clinical Trials Group. Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1995 Sep;13(9):2354-60. [https://doi.org/10.1200/JCO.1995.13.9.2354 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7666094 PubMed]
 
−
# '''SWOG 9028:''' Salmon SE, Crowley JJ, Balcerzak SP, Roach RW, Taylor SA, Rivkin SE, Samlowski W. Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1998 Mar;16(3):890-6. [https://doi.org/10.1200/JCO.1998.16.3.890 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9508170 PubMed]
 
−
# '''HOVON-16:''' Schaar CG, Kluin-Nelemans HC, Te Marvelde C, le Cessie S, Breed WP, Fibbe WE, van Deijk WA, Fickers MM, Roozendaal KJ, Wijermans PW; HOVON. Interferon-alpha as maintenance therapy in patients with multiple myeloma. Ann Oncol. 2005 Apr;16(4):634-9. Epub 2005 Mar 1. [https://doi.org/10.1093/annonc/mdi125 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15741226 PubMed]
 
−
# '''01-002-0601:''' Ludwig H, Hajek R, Tóthová E, Drach J, Adam Z, Labar B, Egyed M, Spicka I, Gisslinger H, Greil R, Kuhn I, Zojer N, Hinke A. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood. 2009 Apr 9;113(15):3435-42. Epub 2008 Oct 27. [https://doi.org/10.1182/blood-2008-07-169565 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18955563 PubMed] NCT00205751
 
−
## '''Update:''' Ludwig H, Adam Z, Tóthová E, Hajek R, Labar B, Egyed M, Spicka I, Gisslinger H, Drach J, Kuhn I, Hinke A, Zojer N. Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma. Haematologica. 2010 Sep;95(9):1548-54. Epub 2010 Apr 23. [http://www.haematologica.org/content/95/9/1548.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20418244 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. [http://www.bloodjournal.org/content/120/8/1589.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22791289 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. [https://doi.org/10.1038/leu.2017.35 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28111466 PubMed]
 
−
==Interferon alfa & Dexamethasone {{#subobject:eed6a1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:304892|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/106/12/3755 Bladé et al. 2005]
 
−
|1994-1999
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: this study did not specify an exact type of interferon alfa.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VBMCP.2FVBAD|VBMCP/VBAD]] x 4, then HDT with [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|MEL200 with auto HSCT]] or [[#Melphalan_.26_TBI.2C_then_auto_HSCT|MEL140 & TBI with auto HSCT]] versus [[#VBMCP.2FVBAD|VBMCP/VBAD]] x 12
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[:Category:Interferons|Inteferon alfa]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div></div>
 
−
===References===
 
−
# 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. [http://www.bloodjournal.org/content/106/12/3755 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16105975 PubMed]
 
−
==Interferon alfa-2b & Prednisone {{#subobject:c007af|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:960322|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.1998.16.3.890 Salmon et al. 1998 (SWOG 9028)]
 
−
|1990-1993
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ooc)
 
−
|[[#Interferon alfa-2b_monotherapy|Interferon alfa-2b]]
 
−
|style="background-color:#1a9850"|Superior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2b (Intron-A)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG 9028:''' Salmon SE, Crowley JJ, Balcerzak SP, Roach RW, Taylor SA, Rivkin SE, Samlowski W. Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol. 1998 Mar;16(3):890-6. [https://doi.org/10.1200/JCO.1998.16.3.890 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9508170 PubMed]
 
−
==Interferon alfa-2b & Thalidomide {{#subobject:46f818|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9e2b82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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-2008-07-169565 Ludwig et al. 2008 (01-002-0601)]
 
−
|2001-2007
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ooc)
 
−
|[[#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]]
 
−
|style="background-color:#1a9850"|Superior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2b (Intron-A)]]
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]]
 
−
</div></div>
 
−
===References===
 
−
# '''01-002-0601:''' Ludwig H, Hajek R, Tóthová E, Drach J, Adam Z, Labar B, Egyed M, Spicka I, Gisslinger H, Greil R, Kuhn I, Zojer N, Hinke A. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood. 2009 Apr 9;113(15):3435-42. Epub 2008 Oct 27. [https://doi.org/10.1182/blood-2008-07-169565 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18955563 PubMed] NCT00205751
 
−
## '''Update:''' Ludwig H, Adam Z, Tóthová E, Hajek R, Labar B, Egyed M, Spicka I, Gisslinger H, Drach J, Kuhn I, Hinke A, Zojer N. Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma. Haematologica. 2010 Sep;95(9):1548-54. Epub 2010 Apr 23. [http://www.haematologica.org/content/95/9/1548.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20418244 PubMed]
 
−
==Prednisolone monotherapy {{#subobject:6a5cf5|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:22bfbf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2008.18.8573 Spencer et al. 2009 (ALLG MM6)]
 
−
|2002-2005
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_.26_Prednisolone|Thalidomide & Prednisolone]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|High-dose melphalan & auto HSCT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 50 mg PO once every other day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===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. -->
 
−
# '''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] '''contains dosing details in manuscript''' [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://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://doi.org/10.1016/S2352-3026(14)00022-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27029229 PubMed]
 
−
==Prednisone monotherapy {{#subobject:ccbda2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, high-dose {{#subobject:43e9a3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/99/9/3163.long Berenson et al. 2002 (SWOG 9210)]
 
−
|1993-1997
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc-ic)
 
−
|[[#Prednisone_monotherapy|Prednisone]]; low-dose
 
−
|style="background-color:#91cf60"|Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma,_induction#VAD-P|VAD-P]] versus [[Multiple_myeloma,_induction#VAD-P.2FQ|VAD-P/Q]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, low-dose {{#subobject:f22c84|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/99/9/3163.long Berenson et al. 2002 (SWOG 9210)]
 
−
|1993-1997
 
−
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
−
|[[#Prednisone_monotherapy|Prednisone]]; high-dose
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Multiple_myeloma,_induction#VAD-P|VAD-P]] versus [[Multiple_myeloma,_induction#VAD-P.2FQ|VAD-P/Q]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 10 mg PO once every other day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM, Barlogie B, Salmon SE. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002 May 1;99(9):3163-8. [http://www.bloodjournal.org/content/99/9/3163.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11964279 PubMed]
 
−
=Relapsed or refractory=
 
−
==Bortezomib monotherapy {{#subobject:eadacb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1 mg/m<sup>2</sup>, 21-day cycle x 8 {{#subobject:77fac1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1365-2141.2004.05188.x Jagannath et al. 2004 (CREST)]
 
−
|2001-2002
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-de-esc)
 
−
|[[#Bortezomib_monotherapy|Bortezomib +/- Dexamethasone]]; 1.3 mg/m<sup>2</sup>
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12198 Petrucci et al. 2013 (RETRIEVE)]
 
−
|2006-NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: RETRIEVE was a re-treatment trial; the dose used was the same as in the initial treatment (1.0 or 1.3 mg/m<sup>2</sup>).''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CREST: 1 to 3 prior therapies, not including bortezomib
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CREST, patients with PD after 2 cycles or SD after 4 cycles: Optional escalation to [[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Dexamethasone_.28VD.29_2|bortezomib & dexamethasone]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1.3 mg/m<sup>2</sup>, 21-day cycle x 8 (IV) {{#subobject:cd7b63|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1111/j.1365-2141.2004.05188.x Jagannath et al. 2004 (CREST)]
 
−
|2001-2002
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc-ic)
 
−
|[[#Bortezomib_monotherapy|Bortezomib +/- Dexamethasone]]; 1 mg/m<sup>2</sup>
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa043445 Richardson et al. 2005 (APEX)]
 
−
|2002-2003
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
−
|[[Multiple_myeloma_-_historical#Dexamethasone_monotherapy_3|High-dose dexamethasone]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<sup>1</sup><br>(HR 0.77)
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12198 Petrucci et al. 2013 (RETRIEVE)]
 
−
|2006-NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.27745 White et al. 2012 (AMBER)]
 
−
|2007-2009
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (C)
 
−
|[[Stub#Bortezomib_.26_Bevacizumab|Bortezomib & Bevacizumab]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70081-X Moreau et al. 2011 (MMY-3021)]
 
−
|2008-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Bortezomib_monotherapy|Bortezomib +/- Dexamethasone]]; SC
 
−
|style="background-color:#eeee01"|Non-inferior ORR
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for APEX is based on the 2007 update.''<br>
 
−
''Note: RETRIEVE was a re-treatment trial; the dose used was the same as in the initial treatment (1.0 or 1.3 mg/m<sup>2</sup>).''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*CREST: 1 to 3 prior therapies, not including bortezomib
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
 
−
====Supportive therapy====
 
−
*[[:Category:Bisphosphonates|Bisphosphonate]] IV therapy once every 3 to 4 weeks unless contraindicated
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CREST, patients with PD after 2 cycles or SD after 4 cycles: Optional escalation to [[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Dexamethasone_.28VD.29_2|bortezomib & dexamethasone]]
 
−
*APEX: [[Multiple_myeloma,_relapsed-refractory#Bortezomib_monotherapy_2|Bortezomib]] consolidation
 
−
*MMY-3021, patients with suboptimal response after 4 cycles: Optional escalation to [[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Dexamethasone_.28VD.29_2|bortezomib & dexamethasone]]
 
−
*MMY-3021, patients who were "evolving" towards CR after 8 cycles: Optional 2 additional cycles (10 total)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1.3 mg/m<sup>2</sup>, 21-day cycle x 8 (SC) {{#subobject:16fb4f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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(11)70081-X Moreau et al. 2011 (MMY-3021)]
 
−
|2008-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 
−
|[[#Bortezomib_monotherapy|Bortezomib +/- Dexamethasone]]; IV
 
−
|style="background-color:#eeee01"|Non-inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> SC once per day on days 1, 4, 8, 11
 
−
**Subcutaneous injections are 2.5 mg/mL (3.5 mg bortezomib reconstituted in 1.4 mL NS)
 
−
**SC injections are in the thighs or abdomen, with injection sites rotated between proximal/distal right/left thigh and upper/lower right/left abdominal quadrants
 
−
====Supportive therapy====
 
−
*[[:Category:Bisphosphonates|Bisphosphonates]] "according to established guidelines"
 
−
'''21-day cycle for 8 cycles (see note)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with suboptimal response after 4 cycles could escalate to [[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Dexamethasone_.28VD.29|bortezomib & dexamethasone]]; patients who were "evolving" towards CR after 8 cycles could receive 2 additional cycles
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 1.3 mg/m<sup>2</sup>, 21-day cycle x 8, then 35-day cycles {{#subobject:cdtjb3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC4737504/ Orlowski et al. 2015 (CR012784)]
 
−
|2006-2009
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (C)
 
−
|[[Stub#Bortezomib_.26_Siltuximab|Bortezomib & Siltuximab]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] as follows:
 
−
**Cycles 1 to 8: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
**Cycle 9 onwards: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''21-day cycle for 8 cycles, then 35-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, indefinite 21-day cycles {{#subobject:e26d0e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa030288 Richardson et al. 2003 (SUMMIT)]
 
−
|2001
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.10.5460 Orlowski et al. 2007 (MMY-3001)]
 
−
|2004-2006
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Pegylated_liposomal_doxorubicin|Bortezomib & PLD]]
 
−
|style="background-color:#d73027"|Inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70398-X Dimopoulos et al. 2013 (VANTAGE 088)]
 
−
|2008-2011
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Vorinostat|Bortezomib & Vorinostat]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: SUMMIT and MMY-3001 specified a total of 8 cycles, but those who were deriving clinical benefit could continue beyond this.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
'''21-day cycles (see note)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SUMMIT & MMY-3001, patients with PD after 2 cycles or SD after 4 cycles: Optional escalation to [[Multiple_myeloma,_relapsed-refractory#Bortezomib_.26_Dexamethasone_.28VD.29|bortezomib & dexamethasone]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 1.6 mg/m<sup>2</sup>, 35-day cycle x 10 {{#subobject:8ug711|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.23606 Hainsworth et al. 2008]
 
−
|2004-2006
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22
 
−
'''35-day cycle for up to 10 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SUMMIT:''' Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17. [https://doi.org/10.1056/NEJMoa030288 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12826635 PubMed]
 
−
## '''Subgroup analysis:''' Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. [http://www.haematologica.org/content/91/7/929.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16818280 PubMed]
 
−
## '''Pooled subgroup analysis:''' Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Cowan JM, Anderson KC. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007 Jan;21(1):151-7. Epub 2006 Nov 9. [https://www.nature.com/articles/2404442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17096017 PubMed]
 
−
# '''CREST:''' Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004 Oct;127(2):165-72. [https://doi.org/10.1111/j.1365-2141.2004.05188.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15461622 PubMed]
 
−
## '''Subgroup Analysis:''' Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. [http://www.haematologica.org/content/91/7/929.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16818280 PubMed]
 
−
## '''Update:''' Jagannath S, Barlogie B, Berenson JR, Siegel DS, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Esseltine DL, Anderson KC. Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib in relapsed or refractory multiple myeloma. Br J Haematol. 2008 Nov;143(4):537-40. Epub 2008 Sep 6. [https://doi.org/10.1111/j.1365-2141.2008.07359.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/18783399 PubMed]
 
−
# '''APEX:''' Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Bladé J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. [https://doi.org/10.1056/NEJMoa043445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15958804 PubMed] NCT00048230
 
−
## '''Pooled subgroup analysis:''' Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Cowan JM, Anderson KC. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007 Jan;21(1):151-7. Epub 2006 Nov 9. [https://www.nature.com/articles/2404442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17096017 PubMed]
 
−
## '''Update:''' Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San Miguel J, Bladé J, Boccadoro M, Cavenagh J, Alsina M, Rajkumar SV, Lacy M, Jakubowiak A, Dalton W, Boral A, Esseltine DL, Schenkein D, Anderson KC. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007 Nov 15;110(10):3557-60. Epub 2007 Aug 9. [http://www.bloodjournal.org/content/110/10/3557.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17690257 PubMed]
 
−
# '''MMY-3001:''' Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. Epub 2007 Aug 6. [https://doi.org/10.1200/jco.2006.10.5460 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17679727 PubMed] NCT00103506
 
−
## '''Update:''' Mikhael JR, Belch AR, Prince HM, Lucio MN, Maiolino A, Corso A, Petrucci MT, Musto P, Komarnicki M, Stewart AK. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol. 2009 Jan;144(2):169-75. Epub 2008 Nov 19. [https://doi.org/10.1111/j.1365-2141.2008.07409.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19036114 PubMed]
 
−
## '''Update:''' Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Xiu L, Cakana A, Parekh T, San-Miguel JF. Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma. Cancer. 2016 Jul 1;122(13):2050-6. Epub 2016 May 18. [https://doi.org/10.1002/cncr.30026 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5701574/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27191689 PubMed]
 
−
# Hainsworth JD, Spigel DR, Barton J, Farley C, Schreeder M, Hon J, Greco FA. Weekly treatment with bortezomib for patients with recurrent or refractory multiple myeloma: a phase 2 trial of the Minnie Pearl Cancer Research Network. Cancer. 2008 Aug 15;113(4):765-71. [https://doi.org/10.1002/cncr.23606 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18543319 PubMed]
 
−
# '''MMY-3021:''' Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, Rekhtman G, Masliak Z, Robak T, Shubina A, Arnulf B, Kropff M, Cavet J, Esseltine DL, Feng H, Girgis S, van de Velde H, Deraedt W, Harousseau JL. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011 May;12(5):431-40. Epub 2011 Apr 18. [https://doi.org/10.1016/S1470-2045(11)70081-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21507715 PubMed] NCT00722566
 
−
## '''Update:''' Arnulf B, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, van de Velde H, Feng H, Cakana A, Deraedt W, Moreau P. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012 Dec;97(12):1925-8. Epub 2012 Jun 11. [http://www.haematologica.org/content/97/12/1925.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685287/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689676 PubMed]
 
−
## '''Subgroup analysis:''' Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Rekhtman G, Masliak Z, Robak P, Esseltine DL, Feng H, Deraedt W, van de Velde H, Arnulf B. Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica. 2015 May;100(5):e207-10. Epub 2015 Jan 16. [http://www.haematologica.org/content/100/5/e207.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420234/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25596270 PubMed]
 
−
# '''AMBER:''' White D, Kassim A, Bhaskar B, Yi J, Wamstad K, Paton VE. Results from AMBER, a randomized phase 2 study of bevacizumab and bortezomib versus bortezomib in relapsed or refractory multiple myeloma. Cancer. 2013 Jan 15;119(2):339-47. Epub 2012 Jul 18. [https://doi.org/full/10.1002/cncr.27745 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22811009 PubMed] NCT00473590
 
−
# '''RETRIEVE:''' Petrucci MT, Giraldo P, Corradini P, Teixeira A, Dimopoulos MA, Blau IW, Drach J, Angermund R, Allietta N, Broer E, Mitchell V, Bladé J. A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma. Br J Haematol. 2013 Mar;160(5):649-59. Epub 2013 Jan 7. [https://doi.org/10.1111/bjh.12198 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23293914 PubMed] NCT00431769
 
−
# '''VANTAGE 088:''' Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-1140. Epub 2013 Sep 19. [https://doi.org/10.1016/S1470-2045(13)70398-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24055414 PubMed] NCT00773747
 
−
# '''CR012784:''' Orlowski RZ, Gercheva L, Williams C, Sutherland H, Robak T, Masszi T, Goranova-Marinova V, Dimopoulos MA, Cavenagh JD, Špička I, Maiolino A, Suvorov A, Bladé J, Samoylova O, Puchalski TA, Reddy M, Bandekar R, van de Velde H, Xie H, Rossi JF. A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. Am J Hematol. 2015 Jan;90(1):42-9. [https://doi.org/10.1002/ajh.23868 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737504/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25294016 PubMed] NCT00401843
 
−
==Carmustine & Doxorubicin {{#subobject:aa6070|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9123b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(76)92710-0 Alberts et al. 1976]
 
−
|1974-1975
 
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
</div></div>
 
−
===References===
 
−
# Alberts DS, Durie BG, Salmon SE. Doxorubicin/BCNU chemotherapy for multiple myeloma in relapse. Lancet. 1976 May 1;1(7966):926-8. [https://doi.org/10.1016/S0140-6736(76)92710-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/57335 PubMed]
 
−
==Dexamethasone monotherapy {{#subobject:dd6070|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, indefinite, high-dose {{#subobject:53824c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1080/10428190902748971 Chanan-Khan et al. 2009 (GENTA-GMY302)]
 
−
|2001-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Oblimersen_.26_Dexamethasone_77|Oblimersen & Dexamethasone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70380-2 San Miguel et al. 2013 (NIMBUS)]
 
−
|2011-2012
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Pd|PD]]
 
−
|style="background-color:#d73027"|Inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy reported for NIMBUS is based on the 2015 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite, weekly {{#subobject:59286c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1007/s00277-019-03739-2 Spicka et al. 2019 (ADMYRE)]
 
−
|2010-2015
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Plitidepsin_.26_Dexamethasone_77|Plitidepsin & Dexamethasone]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*3 to 6 prior lines of therapy, including at least bortezomib and lenalidomide or thalidomide
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, indefinite, with de-escalation {{#subobject:d81270|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa070596 Weber et al. 2007 (MM-009)]
 
−
|2003-2004
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Lenalidomide_.26_Dexamethasone_.28Rd.29|RD]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa070594 Dimopoulos et al. 2007 (MM-010)]
 
−
|2003-2004
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Lenalidomide_.26_Dexamethasone_.28Rd.29|RD]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy of MM-009 is based on the 2009 pooled update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 8 cycles {{#subobject:856d30|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJMoa043445 Richardson et al. 2005 (APEX)]
 
−
|2002-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Bortezomib_monotherapy|Bortezomib]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2007 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycles 5 to 9: 40 mg PO once per day on days 1 to 4
 
−
'''35-day cycle for 4 cycles, then 28-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 12 cycles {{#subobject:d81672|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC3342984/ Kropff et al. 2011 (OPTIMUM)]
 
−
|2006-2009
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[Multiple_myeloma,_relapsed-refractory#Thalidomide_monotherapy|Thalidomide]]; 100 mg/d<br>2. [[Multiple_myeloma,_relapsed-refractory#Thalidomide_monotherapy|Thalidomide]]; 200 mg/d<br> 3. [[Multiple_myeloma,_relapsed-refractory#Thalidomide_monotherapy|Thalidomide]]; 400 mg/d
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
**Cycles 5 to 12: 40 mg PO once per day on days 1 to 4
 
−
'''28-day cycle for up to 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''APEX:''' Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Bladé J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. [https://doi.org/10.1056/NEJMoa043445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15958804 PubMed] NCT00048230
 
−
## '''Pooled subgroup analysis:''' Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Cowan JM, Anderson KC. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007 Jan;21(1):151-7. Epub 2006 Nov 9. [https://www.nature.com/articles/2404442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17096017 PubMed]
 
−
## '''Update:''' Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Miguel JS, Bladé J, Boccadoro M, Cavenagh J, Alsina M, Rajkumar SV, Lacy M, Jakubowiak A, Dalton W, Boral A, Esseltine DL, Schenkein D, Anderson KC. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007 Nov 15;110(10):3557-60. Epub 2007 Aug 9. [http://www.bloodjournal.org/content/110/10/3557.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/17690257 PubMed]
 
−
# '''MM-010:''' Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. [https://doi.org/10.1056/NEJMoa070594 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18032762 PubMed] NCT00424047
 
−
## '''Pooled update:''' Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. Epub 2009 Jul 23. [https://doi.org/10.1038/leu.2009.147 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19626046 PubMed]
 
−
# '''MM-009:''' Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. [https://doi.org/10.1056/NEJMoa070596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18032763 PubMed] NCT00056160
 
−
## '''Pooled update:''' Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. Epub 2009 Jul 23. [https://doi.org/10.1038/leu.2009.147 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19626046 PubMed]
 
−
# '''GENTA-GMY302:''' Chanan-Khan AA, Niesvizky R, Hohl RJ, Zimmerman TM, Christiansen NP, Schiller GJ, Callander N, Lister J, Oken M, Jagannath S. Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma. Leuk Lymphoma. 2009 Apr;50(4):559-65. [https://doi.org/10.1080/10428190902748971 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19373653 PubMed] NCT00017602
 
−
# '''OPTIMUM:''' Kropff M, Baylon HG, Hillengass J, Robak T, Hajek R, Liebisch P, Goranov S, Hulin C, Bladé J, Caravita T, Avet-Loiseau H, Moehler TM, Pattou C, Lucy L, Kueenburg E, Glasmacher A, Zerbib R, Facon T. Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica. 2012 May;97(5):784-91. Epub 2011 Dec 1. [http://www.haematologica.org/content/97/5/784.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342984/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22133776 PubMed] NCT00452569
 
−
# '''NIMBUS:''' San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-66. Epub 2013 Sep 3. [https://doi.org/10.1016/S1470-2045(13)70380-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24007748 PubMed] NCT01311687
 
−
## '''Update:''' Dimopoulos MA, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, Moreau P, Banos A, Oriol A, Garderet L, Cavo M, Ivanova V, Alegre A, Martinez-Lopez J, Chen C, Spencer A, Knop S, Bahlis NJ, Renner C, Yu X, Hong K, Sternas L, Jacques C, Zaki MH, San Miguel JF. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone. Haematologica. 2015 Oct;100(10):1327-33. Epub 2015 Aug 6. [http://www.haematologica.org/content/100/10/1327.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591765/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26250580 PubMed]
 
−
# '''ADMYRE:''' Spicka I, Ocio EM, Oakervee HE, Greil R, Banh RH, Huang SY, D'Rozario JM, Dimopoulos MA, Martínez S, Extremera S, Kahatt C, Alfaro V, Carella AM, Meuleman N, Hájek R, Symeonidis A, Min CK, Cannell P, Ludwig H, Sonneveld P, Mateos MV. Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs dexamethasone alone in patients with relapsed/refractory multiple myeloma. Ann Hematol. 2019 Sep;98(9):2139-2150. Epub 2019 Jun 25. [https://doi.org/10.1007/s00277-019-03739-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31240472 PubMed] NCT01102426
 
−
==EDAP {{#subobject:d0dadc|Regimen=1}}==
 
−
EDAP: '''<u>E</u>'''toposide, '''<u>D</u>'''examethasone, '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5864a9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1989.7.10.1514 Barlogie et al. 1989]
 
−
|NR
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]]
 
−
*[[Cytarabine (Ara-C)]]
 
−
*[[Cisplatin (Platinol)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
</div></div>
 
−
===References===
 
−
# Barlogie B, Velasquez WS, Alexanian R, Cabanillas F. Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma. J Clin Oncol. 1989 Oct;7(10):1514-7. [https://doi.org/10.1200/JCO.1989.7.10.1514 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2778481 PubMed]
 
−
==Melphalan flufenamide & Dexamethasone {{#subobject:0f8gua|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:34ug71|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.20.02259 Richardson et al. 2020 (HORIZON<sub>RRMM</sub>)]
 
−
|2016-2019
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(21)00381-1 Schjesvold et al. 2022 (OCEAN)]
 
−
|2017-2020
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Pomalidomide_.26_Dexamethasone_.28PD.29|PD]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 6.8 vs 4.9 mo<br>(HR 0.79, 95% CI 0.64-0.98)
 
−
|-
 
−
|}
 
−
''Note: this variant is intended for patients 75 or younger. HORIZON should not be confused with the trial by the same name in breast cancer.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Peptide-drug conjugate therapy====
 
−
*[[Melphalan flufenamide (Pepaxto)]] 40 mg IV over 30 minutes once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:34ig81|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.20.02259 Richardson et al. 2020 (HORIZON<sub>RRMM</sub>)]
 
−
|2016-2019
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(21)00381-1 Schjesvold et al. 2022 (OCEAN)]
 
−
|2017-2020
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[Multiple_myeloma,_relapsed-refractory#Pomalidomide_.26_Dexamethasone_.28PD.29|PD]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 6.8 vs 4.9 mo<br>(HR 0.79, 95% CI 0.64-0.98)
 
−
|-
 
−
|}
 
−
''Note: this variant is intended for patients older than 75. HORIZON should not be confused with the trial by the same name in breast cancer.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Peptide-drug conjugate therapy====
 
−
*[[Melphalan flufenamide (Pepaxto)]] 40 mg IV over 30 minutes once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''HORIZON:''' Richardson PG, Oriol A, Larocca A, Bladé J, Cavo M, Rodriguez-Otero P, Leleu X, Nadeem O, Hiemenz JW, Hassoun H, Touzeau C, Alegre A, Paner A, Maisel C, Mazumder A, Raptis A, Moreb JS, Anderson KC, Laubach JP, Thuresson S, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Mateos MV; HORIZON (OP-106) Investigators. Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma. J Clin Oncol. 2021 Mar 1;39(7):757-767. Epub 2020 Dec 9. [https://doi.org/10.1200/jco.20.02259 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33296242/ PubMed] NCT02963493
 
−
# '''OCEAN:''' Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Špička I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosiñol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hájek R, Mateos MV, Richardson PG, Sonneveld P; OCEAN (OP-103) Investigators. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022 Feb;9(2):e98-e110. Epub 2022 Jan 12. [https://doi.org/10.1016/s2352-3026(21)00381-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35032434/ PubMed] NCT03151811
 
−
==Pomalidomide, Dexamethasone, Pembrolizumab {{#subobject:6192e0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:dd976e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/130/10/1189.long Badros et al. 2017 (1454GCC)]
 
−
|2015-2016
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#9ebcda" |ORR: 60%
 
−
|-
 
−
|}
 
−
''Note: This is of historical interest only, at this time. While the phase 2 had a high degree of efficacy (thus meeting our inclusion criteria), subsequent phase 3 trials were halted by the FDA for excess deaths in this arm; see "Note added in proof" in the paper for more details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pomalidomide (Pomalyst)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]]
 
−
</div></div>
 
−
===References===
 
−
# '''1454GCC:''' Badros A, Hyjek E, Ma N, Lesokhin A, Dogan A, Rapoport AP, Kocoglu M, Lederer E, Philip S, Milliron T, Dell C, Goloubeva O, Singh Z. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1189-1197. Epub 2017 May 1. [http://www.bloodjournal.org/content/130/10/1189.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/28461396 PubMed] NCT02289222
 
−
==Stilbamidine & Urethane {{#subobject:d9gub4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:60chb9|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(47)90375-9 Alwall 1947]
 
−
|style="background-color:#ffffbe"|Case series
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Stilbamidine]]
 
−
*[[Urethane]]
 
−
</div></div>
 
−
===References===
 
−
#'''Case series:''' Alwall N. Urethane and stilbamidine in multiple myeloma report on two cases. Lancet. 1947 Sep 13;2(6472):388. [https://doi.org/10.1016/s0140-6736(47)90375-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20263550 PubMed]
 
−
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:60fc19|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646711/ Garfall et al. 2015 (UPCC02413)]
 
−
|style="background-color:#ffffbe"|Pilot, 1 patient
 
−
|-
 
−
|}
 
−
''Note: this regimen is of historic interest in this context. It is not FDA approved for this indication.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Tisagenlecleucel (Kymriah)]]
 
−
</div></div>
 
−
===References===
 
−
# '''UPCC02413:''' Garfall AL, Maus MV, Hwang WT, Lacey SF, Mahnke YD, Melenhorst JJ, Zheng Z, Vogl DT, Cohen AD, Weiss BM, Dengel K, Kerr ND, Bagg A, Levine BL, June CH, Stadtmauer EA. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. N Engl J Med. 2015 Sep 10;373(11):1040-7. [https://doi.org/10.1056/NEJMoa1504542 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646711/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26352815 PubMed] NCT02135406
 
−
==Urethane monotherapy {{#subobject:9ihjbsb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:91tjg2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1001/jama.1951.03670260026008 Luttgens et al. 1951]
 
−
|1948-1950
 
−
| style="background-color:#ffffbe" |Case series
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1182/blood.V27.3.328.328 Holland et al. 1966]
 
−
|1958-1961
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[Multiple_myeloma_-_null_regimens#Placebo_2|Placebo]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Urethane]]
 
−
</div></div>
 
−
===References===
 
−
# Luttgens WF, Bayrd ED. Treatment of multiple myeloma with urethan: experience with sixty-six cases over a two-and-a-half-year period. JAMA. 1951 Oct;147(9):824-7. [https://doi.org/10.1001/jama.1951.03670260026008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14873565/ PubMed]
 
−
#Holland JF, Hosley H, Scharlau C, Carbone PP, Frei E 3rd, Brindley CO, Hall TC, Shnider BI, Gold GL, Lasagna L, Owens AH Jr, Miller SP. A controlled trial of urethane treatment in multiple myeloma. Blood. 1966 Mar;27(3):328-42. [https://doi.org/10.1182/blood.V27.3.328.328 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5933438 PubMed]
 
−
==VAD {{#subobject:9cab6b|Regimen=1}}==
 
−
VAD: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<br>VAd: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), low-dose '''<u>d</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3541e2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/NEJM198405243102104 Barlogie et al. 1984]
 
−
|1983
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142%2819950201%2975%3A3%3C815%3A%3AAID-CNCR2820750311%3E3.0.CO%3B2-R Dalton et al. 1995 (SWOG S8900)]
 
−
|1988-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#VAD.2Fv_99|VAD/v]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
|}
 
−
''Note: Treatment was given "until a maximum reduction in myeloma protein had occurred" and patients received four additional cycles of therapy beyond their best response.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
====Supportive therapy====
 
−
*[[Cimetidine (Tagamet)]] prophylaxis (dose not specified)
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] prophylaxis (dose not specified)
 
−
'''35-day cycles (see note)'''
 
−
</div></div>
 
−
===References===
 
−
# Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med. 1984 May 24;310(21):1353-6. [https://doi.org/10.1056/NEJM198405243102104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6546971 PubMed]
 
−
# '''SWOG S8900:''' Dalton WS, Crowley JJ, Salmon SS, Grogan TM, Laufman LR, Weiss GR, Bonnet JD. A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma: a Southwest Oncology Group study. Cancer. 1995 Feb 1;75(3):815-20. [https://doi.org/10.1002/1097-0142%2819950201%2975%3A3%3C815%3A%3AAID-CNCR2820750311%3E3.0.CO%3B2-R link to original article] [https://pubmed.ncbi.nlm.nih.gov/7828131 PubMed]
 
−
==VAD & Cyclosporine {{#subobject:9b3d6b|Regimen=1}}==
 
−
VAD & Cyclosporine: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone, Cyclosporine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1341e2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1016/0140-6736(92)92353-H Sonneveld et al. 1992]
 
−
|NR
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/full/10.1046/j.1365-2141.2001.03171.x Sonneveld et al. 2001 (EORTC 06914)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 2/3 (E-esc-ooc)
 
−
|[[#VAD_2|VAD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of best RR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]]
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine|Cyclosporine]]
 
−
</div></div>
 
−
===References===
 
−
# Sonneveld P, Durie BG, Lokhorst HM, Marie JP, Solbu G, Suciu S, Zittoun R, Löwenberg B, Nooter K; EORTC; HOVON. Modulation of multidrug-resistant multiple myeloma by cyclosporin. Lancet. 1992 Aug 1;340(8814):255-9. [https://doi.org/10.1016/0140-6736(92)92353-H link to original article] [https://pubmed.ncbi.nlm.nih.gov/1353189 PubMed]
 
−
# '''EORTC 06914:''' Sonneveld P, Suciu S, Weijermans P, Beksac M, Neuwirtova R, Solbu G, Lokhorst H, van der Lelie J, Dohner H, Gerhartz H, Segeren CM, Willemze R, Lowenberg B; [[Study_Groups#EORTC|EORTC]]; Leukaemia Cooperative Group; HOVON. Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914). Br J Haematol. 2001 Dec;115(4):895-902. [https://doi.org/full/10.1046/j.1365-2141.2001.03171.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/11843823 PubMed]
 
−
[[Category:Multiple myeloma regimens]]
 
−
[[Category:Historical regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Plasma cell dyscrasias]]
 

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