Difference between revisions of "Multiple myeloma"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
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{{#lst:Editorial board transclusions|pcd}}
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Multiple_myeloma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Multiple myeloma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br>
 +
<br>'''Note: due to its size/complexity, the multiple myeloma page has been split into sub-pages:'''
 +
*[[Multiple_myeloma,_induction|Induction (transplant eligible and ineligible)]]
 +
*[[Multiple_myeloma,_consolidation_and_maintenance|First-line consolidation and maintenance]]
 +
*[[Multiple_myeloma,_relapsed-refractory|Relapsed/refractory, including subsequent consolidation and maintenance]]
 +
*[[Smoldering multiple myeloma]]
 +
'''This page will remain as a consolidated location for guidelines and prognostic information.
  
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]] ''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Multiple_myeloma_-_obsolete|obsolete regimens page]]. If you still can't find it, please let us know so we can add it!''.
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*''We have moved [[How I Treat]] articles to a dedicated page.''
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|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
 
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<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
 
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<section begin=guidelines />
 
=Guidelines=
 
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
  
−
==BSH/UKMF==
+
==[https://www.asco.org ASCO]/CCO==
−
===Current===
+
*'''2019:''' Mikhael et al. [https://doi.org/10.1200/jco.18.02096 Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/30932732/ PubMed]
−
*[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14827/full Guidelines for the use of imaging in the management of patients with myeloma (2017)] [https://www.ncbi.nlm.nih.gov/pubmed/28677897 PubMed]
+
*'''2018:''' Anderson et al. [https://doi.org/10.1200/JCO.2017.76.6402 Role of bone-modifying agents in multiple myeloma: American Society of Clinical Oncology Clinical Practice Guideline update] [https://pubmed.ncbi.nlm.nih.gov/29341831/ PubMed]
−
*[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14514/abstract Guidelines for screening and management of late and long-term consequences of myeloma and its treatment (2017)] [https://www.ncbi.nlm.nih.gov/pubmed/28107574 PubMed]
+
**'''2007:''' Kyle et al. [https://doi.org/10.1200/jco.2007.12.1269 American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma] [https://pubmed.ncbi.nlm.nih.gov/17515569/ PubMed]
−
*[http://www.ukmf.org.uk/wp-content/uploads/2014/10/Updates-to-the-guidelines-Oct-2014.pdf Updates to the guidelines for the diagnosis and management of multiple myeloma (2014)] [https://www.ncbi.nlm.nih.gov/pubmed/24801672 PubMed]
+
**'''2002:''' Berenson et al. [https://doi.org/10.1200/jco.2002.06.037 American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma] [https://pubmed.ncbi.nlm.nih.gov/12202673/ PubMed]
  
−
==ESMO==
+
==[http://www.b-s-h.org.uk/ BSH]/[http://www.ukmf.org.uk/ UKMF]==
−
*[https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdx096 Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2017)]
+
*'''2017:''' [https://doi.org/10.1111/bjh.14827 Guidelines for the use of imaging in the management of patients with myeloma] [https://pubmed.ncbi.nlm.nih.gov/28677897/ PubMed]
 +
*'''2017:''' [https://doi.org/10.1111/bjh.14514 Guidelines for screening and management of late and long-term consequences of myeloma and its treatment] [https://pubmed.ncbi.nlm.nih.gov/28107574/ PubMed]
 +
*'''2014:''' [http://www.ukmf.org.uk/wp-content/uploads/2014/10/Updates-to-the-guidelines-Oct-2014.pdf Updates to the guidelines for the diagnosis and management of multiple myeloma] [https://pubmed.ncbi.nlm.nih.gov/24801672/ PubMed]
 +
**'''2011:''' [https://doi.org/10.1111/bjh.12926 Guidelines for the diagnosis and management of multiple myeloma 2011] [https://pubmed.ncbi.nlm.nih.gov/24801672/ PubMed]
  
−
==NCCN==
+
==[http://myeloma-europe.org.linux9.curanetserver.dk/index.php European Myeloma Network (EMN)]==
−
*[https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf NCCN Guidelines - Multiple Myeloma]
+
*'''2020:''' Ludwig et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7787974/ Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network] [https://pubmed.ncbi.nlm.nih.gov/32814840/ PubMed]
 +
*'''2018:''' Caers et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6278986/ European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when] [https://pubmed.ncbi.nlm.nih.gov/30171031/ PubMed]
 +
*'''2018:''' Gay et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5792264/ From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives] [https://pubmed.ncbi.nlm.nih.gov/29217780/ PubMed]
  
−
=Untreated (including transplant ineligible), randomized data=
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==EHA/[https://www.esmo.org/ ESMO]==
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''Note: most but not all multiple myeloma first-line regimens specify whether patients are transplant eligible, or not. The top-line inclusion criteria from each prospectively enrolling regimen are reported.''
+
*'''2021:''' Dimopoulos et al. [https://doi.org/10.1016/j.annonc.2020.11.014 Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/33549387/ PubMed]
 +
**'''2017:''' Moreau et al. [https://doi.org/10.1093/annonc/mdx096 Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/23956208/ PubMed]
 +
**'''2013:''' Moreau et al. [https://doi.org/10.1093/annonc/mdt297 Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/23956208/ PubMed]
 +
**'''2010:''' Harousseau & Dreyling. [https://doi.org/10.1093/annonc/mdq178 Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555068/ PubMed]
 +
**'''2009:''' Harousseau & Dreyling. [https://doi.org/10.1093/annonc/mdp140 Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454476/ PubMed]
 +
**'''2008:''' Harousseau & Dreyling. [https://doi.org/10.1093/annonc/mdn088 Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456769/ PubMed]
 +
**'''2007:''' Harousseau. [https://doi.org/10.1093/annonc/mdm032 Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491042/ PubMed]
 +
**'''2005:''' Harousseau et al. [https://doi.org/10.1093/annonc/mdi818 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of multiple myeloma] [https://pubmed.ncbi.nlm.nih.gov/15888750/ PubMed]
  
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==Bort-Dex {{#subobject:b2104f|Regimen=1}}==
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==[http://imwg.myeloma.org/ IMWG]==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
*'''2021:''' Moreau et al. [https://doi.org/10.1016/S1470-2045(20)30756-7 Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group] [https://pubmed.ncbi.nlm.nih.gov/33662288 PubMed]
−
|-
+
*'''2021:''' Terpos et al. [https://doi.org/10.1016/S1470-2045(20)30559-3 Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group] [https://pubmed.ncbi.nlm.nih.gov/33545067/ PubMed]
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|[[#top|back to top]]
 
−
|}
 
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BD: '''<u>B</u>'''ortezomib, '''<u>D</u>'''examethasone
 
−
<br>Bd: '''<u>B</u>'''ortezomib, low-dose '''<u>d</u>'''examethasone
 
−
<br>Bort-Dex: '''<u>Bort</u>'''ezomib, '''<u>Dex</u>'''amethasone
 
−
<br>Vd: '''<u>V</u>'''elcade (Bortezomib), low-dose '''<u>d</u>'''examethasone
 
−
<br>VD: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone
 
  
−
===Regimen #1 {{#subobject:59cfe6|Variant=1}}===
+
*'''2016:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920674/ Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group] [https://pubmed.ncbi.nlm.nih.gov/27002115 PubMed]
−
{| border="1" style="text-align:center;" !align="left"
+
*'''2016:''' [https://doi.org/10.1200/JCO.2015.65.0044 International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment] [https://pubmed.ncbi.nlm.nih.gov/26976420/ PubMed]
−
|'''Study'''
+
*'''2014:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918540/ International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation] [https://pubmed.ncbi.nlm.nih.gov/24419113/ PubMed]
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|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
*'''2013:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878084/ International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease] [https://pubmed.ncbi.nlm.nih.gov/23690408/ PubMed]
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|rowspan=2|[http://jco.ascopubs.org/content/33/33/3921.long Niesvizky et al. 2015 (UPFRONT)]
 
−
|rowspan=2 style="background-color:#00cd00"|Phase III
 
−
|[[#VMP|VMP]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|[[#VTD|VTD]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|}
 
  
−
''This regimen was meant for transplant ineligible patients.''
+
==NCCN==
−
====Chemotherapy====
+
*[https:
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 to 4: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
**Cycles 5 to 8: 20 mg PO once per day on days 1, 2, 4, 5
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
''Treatment followed by [[#Bortezomib_monotherapy|bortezomib maintenance]].''
 
−
 
 
−
===Regimen #2 {{#subobject:6a8cb5|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/22/5752.full Moreau et al. 2011 (IFM 2007-02)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#VTD|vtD]]
 
−
|style="background-color:#d73027"|Inferior VGPR rate
 
−
|-
 
−
|}
 
−
''This regimen was intended for patients aged 65 years or younger with untreated symptomatic MM with measurable paraprotein in serum (greater than 1 g/dL) or urine (greater than 0.2 g/24 hours).''
 
−
====Chemotherapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2: 40 mg (route not specified) once per day on days 1 to 4, 9 to 12
 
−
**Cycles 3 & 4: 40 mg (route not specified) once per day on days 1 to 4
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
''All patients then underwent [[#Melphalan.2C_then_autologous_hematopoietic_cell_transplant|high dose melphalan, then autologous hematopoietic cell transplant]].''
 
−
 
 
−
===Regimen #3 {{#subobject:9d60fb|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://jco.ascopubs.org/content/28/30/4621.long Harousseau et al. 2010 (IFM 2005-01)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[Multiple_myeloma_-_obsolete#VAD|VAD]]
 
−
|style="background-color:#d9ef8b"|Might have superior PFS
 
−
|-
 
−
|}
 
−
''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 g/dL) or urine (greater than 0.2 g/24 h).''
 
−
====Chemotherapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12
 
−
**Cycles 3 & 4: 40 mg PO once per day on days 1 to 4
 
−
 
 
−
====Supportive medications====
 
−
*One of the following bisphosphonates recommended:
 
−
**[[Pamidronate (Aredia)]] 90 mg IV once every 4 weeks until first transplant
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV once every 4 weeks until first transplant
 
−
*"Antibiotics, antifungal agents, and antiviral prophylaxis in accordance with local practice."
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
''Patients were then randomized to [[#DCEP|DCEP consolidation]] or went directly to [[#Melphalan.2C_then_autologous_hematopoietic_cell_transplant|autologous hematopoietic cell transplant]].''
 
−
 
 
−
===Regimen #4, weekly bortezomib {{#subobject:5f56bd|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13243/full Girnius et al. 2014]
 
−
|style="background-color:#eeee00"|Phase II
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per week on days 1, 8, 15, 22
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
 
 
−
'''35-day cycle for up to 6 cycles based on response and tolerance of side effects'''
 
−
 
 
−
===References===
 
−
<!-- Presented at the 48th Annual Meeting of the American Society of Hematology (ASH), December 9-12, 2006, Orlando, FL; the 49th Annual Meeting of the ASH, December 8-11, 2007, Atlanta, GA; the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30-June 3, 2008, Chicago, IL; and the 2008 Annual Meeting of the American Society of Hematology ASH/ASCO Joint Symposium, December 7, 2008, San Francisco, CA. -->
 
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# 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. [http://jco.ascopubs.org/content/28/30/4621.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20823406 PubMed]
 
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## '''Subgroup analysis:''' Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D, Marit G, Benboubker L, Voillat L, Mathiot C, Kolb B, Macro M, Campion L, Wetterwald M, Stoppa AM, Hulin C, Facon T, Attal M, Minvielle S, Harousseau JL. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010 Oct 20;28(30):4630-4. Epub 2010 Jul 19. [http://jco.ascopubs.org/content/28/30/4630.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20644101 PubMed]
 
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# Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. [http://www.bloodjournal.org/content/118/22/5752.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21849487 PubMed]
 
−
# Girnius SK, Lee S, Kambhampati S, Rose MG, Mohiuddin A, Houranieh A, Zimelman A, Grady T, Mehta P, Behler C, Hayes TG, Efebera YA, Prabhala RH, Han A, Yellapragada SV, Klein CE, Roodman GD, Lichtenstein A, Munshi NC. A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation. Br J Haematol. 2015 Apr;169(1):36-43. Epub 2015 Jan 8. Epub 2014 Sep 18. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13243/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25572917 PubMed]
 
−
<!-- Presented at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011; and the 55th ASH Annual Meeting and Exposition, New Orleans, LA, December 7-10, 2013. -->
 
−
# Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol. 2015 Nov 20;33(33):3921-9. Epub 2015 Jun 8. [http://jco.ascopubs.org/content/33/33/3921.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26056177 PubMed]
 
−
 
 
−
==CPR {{#subobject:6ec39f|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
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|-
 
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|[[#top|back to top]]
 
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CPR: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone, '''<u>R</u>'''evlimid (Lenalidomide)
 
−
 
 
−
===Regimen {{#subobject:7999a2|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|rowspan=2|[http://www.bloodjournal.org/content/127/9/1102.long Magarotto et al. 2016 (EMN01)]
 
−
|rowspan=2 style="background-color:#00cd00"|Phase III
 
−
|[[#MPR|MPR]]
 
−
|style="background-color:#fee08b"|Might have inferior PFS
 
−
|-
 
−
|[[#Rd|Rd]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|}
 
−
''This regimen is intended for patients who were ineligible for high-dose therapy plus stem cell transplantation because of age (greater than or equal to 65 years) or coexisting comorbidities. This is the dosing used after a mid-protocol amendment.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day on days 1 to 21
 
−
*[[Prednisone (Sterapred)]] 25 mg PO once every other day
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
 
 
−
====Supportive medications====
 
−
*[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] at physician's discretion (mandatory)
 
−
 
 
−
'''28-day cycle for 9 cycles'''
 
−
 
 
−
''Patients were then randomized to [[#Lenalidomide_monotherapy|lenalidomide maintenance]] versus [[#Lenalidomide_.26_Prednisone_2|lenalidomide & prednisone maintenance]].''
 
−
 
 
−
===References===
 
−
# Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. Epub 2016 Jan 4. [http://www.bloodjournal.org/content/127/9/1102.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26729895 PubMed]
 
−
 
 
−
==CTD {{#subobject:658a40|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
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CTD: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
<br>CTDa: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone, '''<u>a</u>'''ttenuated
 
−
 
 
−
===Regimen #1, CTD {{#subobject:e5fcc6|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/1/7.long Morgan et al. 2011 (MRC Myeloma IX)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#CVAD|CVAD]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|}
 
−
''This is an intensive treatment pathway, as determined by performance status, informed discussion, and patient preference.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg PO once per week
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 21, increasing to 200 mg PO once per day "if tolerated"
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 12 to 15
 
−
 
 
−
====Supportive medications====
 
−
*Venous thromboembolism (VTE) prophylaxis was given at physician discretion, but it was suggested that low-risk patients receive [[Aspirin]] and high-risk patients receive [[Warfarin (Coumadin)]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]] according to risk categories as described by ''Palumbo A et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23. [http://www.nature.com/leu/journal/v22/n2/full/2405062a.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18094721 PubMed]''
 
−
*Patients in the study were randomized to 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
 
−
 
 
−
'''21-day cycle for 4 to 6 cycles until maximum response'''
 
−
 
 
−
''All responding patients proceeded to [[#Melphalan.2C_then_autologous_hematopoietic_cell_transplant|high-dose melphalan and autologous hematopoietic cell transplant]].''
 
−
 
 
−
===Regimen #2, CTDa {{#subobject:db34fc|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152492/ Morgan et al. 2011 (MRC Myeloma IX)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#MP|MP]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|}
 
−
 
 
−
''This is a nonintensive treatment pathway, as determined by performance status, informed discussion, and patient preference.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg PO once per week
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 28; dose is increased every 4 weeks in 50 mg increments, up to a maximum dose of 200 mg PO once per day
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 15 to 18
 
−
 
 
−
====Supportive medications====
 
−
*For the first 12 weeks of treatment, thromboprophylaxis--for example, with [[Warfarin (Coumadin)]] or [[:Category:Low molecular weight heparins|low molecular weight heparin]]--was recommended
 
−
*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'''
 
−
 
 
−
''Patients were then randomized to [[#Thalidomide_monotherapy|thalidomide maintenance]] versus [[#Observation|no further treatment]].''
 
−
 
 
−
===References===
 
−
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291601/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/23995858 PubMed]
 
−
 
 
−
==CVAD {{#subobject:c3a1db|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
CVAD: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen {{#subobject:51a834|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/1/7.long Morgan et al. 2011 (MRC Myeloma IX)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#CTD|CTD]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|}
 
−
''This is an intensive treatment pathway, as determined by performance status, informed discussion, and patient preference.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg PO once per day on days 1, 8, 15
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day IV continuous infusion on days 1 to 4 (total dose per cycle: 1.6 mg)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 12 to 15
 
−
 
 
−
====Supportive medications====
 
−
*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
 
−
 
 
−
'''21-day cycle for 4 to 6 cycles until maximum response'''
 
−
 
 
−
''All responding patients proceeded to [[#Melphalan.2C_then_autologous_hematopoietic_cell_transplant|high-dose melphalan and autologous hematopoietic cell transplant]].''
 
−
 
 
−
===References===
 
−
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291601/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/23995858 PubMed]
 
−
 
 
−
==Dexamethasone monotherapy {{#subobject:b86fb2|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen #1, indefinite with 35-day induction cycles {{#subobject:05800b|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031379/ Zonder et al. 2010 (SWOG S0232)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#Rd|Len-Dex]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
''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.''
 
−
====Chemotherapy====
 
−
*[[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 of a 35-day cycle
 
−
**Cycle 4 onwards: 40 mg PO once per day on days 1 to 4
 
−
 
 
−
====Supportive medications====
 
−
*[[Aspirin]] 325 mg PO once per day unless already on anticoagulation therapy
 
−
 
 
−
'''28-day cycles (*)'''
 
−
 
 
−
===Regimen #2, indefinite with 28-day induction cycles {{#subobject:21bfc9|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904367/ Rajkumar et al. 2008]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#Thal-Dex|TD]]
 
−
|style="background-color:#d73027"|Inferior TTP
 
−
|-
 
−
|}
 
−
''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.''
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
 
 
−
===Regimen #3, indefinite with alternating dexamethasone intensity {{#subobject:bb3ebb|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|[[Levels_of_Evidence#Toxicity|'''Toxicity''']]
 
−
|-
 
−
|[http://jco.ascopubs.org/content/24/3/431.long Rajkumar et al. 2005]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|[[#Thal-Dex|TD]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior RR
 
−
|style="background-color:#1a9850"|Superior toxicity
 
−
|-
 
−
|}
 
−
 
 
−
''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.''
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
 
 
−
===Regimen #4, 12 cycles total {{#subobject:5be1f9|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|rowspan = "2" | [http://www.bloodjournal.org/content/107/4/1292.long Facon et al. 2005 (IFM 95-01)]
 
−
|rowspan = "2" style="background-color:#00cd00"|Phase III
 
−
|[[#DEX-IFN|DEX-IFN]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|[[#MP|MP]]<br> [[#M-DEX|M-DEX]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
 
 
−
''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 [[#Durie-Salmon_Staging_System_-_1975|Durie and Salmon criteria]]. Some stage I patients were allowed; see text for details.''
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
 
 
−
===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 (IFM) group. 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 protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16174762 PubMed]
 
−
# Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group. 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. [http://jco.ascopubs.org/content/24/3/431.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16365178 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/26/13/2171.long link to original article] '''contains verified protocol''' [https://www.
 
  
−
==Thalidomide monotherapy {{#subobject:ff02e1|Regimen=1}}==
+
==SITC==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
*'''2020:''' Shah et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7359060/ The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma] [https://pubmed.ncbi.nlm.nih.gov/32661116/ PubMed]
−
|-
+
<section end=guidelines />
−
|[[#top|back to top]]
+
<section begin=bottom />
−
|}
 
−
 
 
−
===Regimen {{#subobject:43a4e3|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://www.nejm.org/doi/full/10.1056/NEJM199911183412102 Singhal et al. 1999]
 
−
|style="background-color:#eeee00"|Non-randomized
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day, increased by 200 mg every two weeks for six weeks, to final dose of 800 mg per day
 
−
 
 
−
'''Continued until progression'''
 
−
 
 
−
===References===
 
−
# Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. [http://www.nejm.org/doi/full/10.1056/NEJM199911183412102 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10564685 PubMed]
 
−
 
 
−
==Vemurafenib monotherapy {{#subobject:c957e9|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:5b6425|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://cancerdiscovery.aacrjournals.org/content/3/8/862.long Andrulis et al. 2013]
 
−
|style="background-color:#ff0000"|Case report
 
−
|-
 
−
|}
 
−
 
 
−
''Note that Andrulis et al. 2013 is a single patient case report with a good response. Sharman et al. reports two patients with good response. In the Hyman et al. 2015 trial, there were 5 patients with multiple myeloma; "No patients with multiple myeloma have had a response to date."''
 
−
====Chemotherapy====
 
−
*[[Vemurafenib (Zelboraf)]] 480 mg PO BID for one week, then increased to 720 mg PO BID
 
−
 
 
−
===References===
 
−
# Andrulis M, Lehners N, Capper D, Penzel R, Heining C, Huellein J, Zenz T, von Deimling A, Schirmacher P, Ho AD, Goldschmidt H, Neben K, Raab MS. Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov. 2013 Aug;3(8):862-9. Epub 2013 Apr 23. [http://cancerdiscovery.aacrjournals.org/content/3/8/862.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23612012 PubMed]
 
−
# Sharman JP, Chmielecki J, Morosini D, Palmer GA, Ross JS, Stephens PJ, Stafl J, Miller VA, Ali SM. Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma. Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):e161-3. Epub 2014 Jun 11. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00138-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24997557 PubMed]
 
−
# Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-36. [http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26287849 PubMed]
 
−
 
 
−
==VMPT {{#subobject:c7cda5|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
VMPT: '''<u>V</u>'''elcade (Bortezomib), '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>T</u>'''halidomide
 
−
 
 
−
===Regimen {{#subobject:d55f41|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/109/7/2767.full Palumbo et al. 2007]
 
−
|style="background-color:#eeee00"|Phase II
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Bortezomib (Velcade)]] 1 to 1.3 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 15, 22
 
−
*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 35
 
−
 
 
−
'''35-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, Cangialosi C, Caravita T, Morabito F, Musto P, Bringhen S, Falco P, Avonto I, Cavallo F, Boccadoro M; Italian Multiple Myeloma Network; Gruppo Italiano Malattie Ematologicche dell'Adulto. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood. 2007 Apr 1;109(7):2767-72. [http://www.bloodjournal.org/content/109/7/2767.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17148584 PubMed]
 
−
 
 
−
==Vorinostat, Lenalidomide, Dexamethasone {{#subobject:4e6061|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:0c164a|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14429/abstract Sanchez et al. 2016]
 
−
|style="background-color:#eeee00"|Phase IIb
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vorinostat (Zolinza)]] 400 mg PO once per day on days 1 to 7, 15 to 21
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per week on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Sanchez L, Vesole DH, Richter JR, Biran N, Bilotti E, McBride L, Anand P, Ivanovski K, Siegel DS. A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens. Br J Haematol. 2017 Feb;176(3):440-447. Epub 2016 Nov 18. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14429/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27859001 PubMed]
 
−
 
 
−
=Consolidation after salvage therapy=
 
−
 
 
−
==Melphalan, then autologous hematopoietic cell transplant {{#subobject:149d91|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:83243a|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
−
|-
 
−
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70245-1/fulltext Cook et al. 2014 (NCRI Myeloma X Relapse)]
 
−
|style="background-color:#00cd00"|Phase III
 
−
|Cyclophosphamide
 
−
|style="background-color:#91cf60"|Seems to have superior OS (*)
 
−
|-
 
−
|}
 
−
''Treatment preceded by [[#PAD_2|PAD]] x 4. Efficacy reported is based on the 2016 update.''
 
−
====Preparative regimen====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m<sup>2</sup> IV on day -2
 
−
 
 
−
'''Stem cells re-infused on day 0'''
 
−
 
 
−
===References===
 
−
# Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, Ashcroft AJ, Fletcher M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Chalmers A, O'Connor S, Drayson MT, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):874-85. Epub 2014 Jun 16. Erratum in: Lancet Oncol. 2014 Aug;15(9):e365. Dosage error in article text. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70245-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24948586 PubMed]
 
−
## '''Update:''' Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, Snowden JA, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Chown S, Heartin E, O'Connor S, Drayson MT, Hockaday A, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016 Jul;3(7):e340-51. [http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30049-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27374467 PubMed]
 
−
 
 
−
=Maintenance after salvage therapy=
 
−
 
 
−
==Bortezomib & Cyclophosphamide {{#subobject:eaadfe|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:5e9a21|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13653/full de Waal et al. 2015]
 
−
|style="background-color:#eeee00"|Phase II
 
−
|-
 
−
|}
 
−
 
 
−
''Treatment preceded by [[#Bortezomib.2C_Cyclophosphamide.2C_Dexamethasone|bortezomib, cyclophosphamide, dexamethasone]] x 6.''
 
−
====Chemotherapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV/SC every 2 weeks
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day (continuous)
 
−
 
 
−
====Supportive medications====
 
−
*Pneumococccal and anti-fungal prophylaxis "according to local protocols"
 
−
*[[Valacyclovir (Valtrex)]] (dose not specified) for herpes prophylaxis
 
−
 
 
−
'''1-year course'''
 
−
 
 
−
===References===
 
−
# de Waal EG, de Munck L, Hoogendoorn M, Woolthuis G, van der Velden A, Tromp Y, Vellenga E, Hovenga S. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients. Br J Haematol. 2015 Dec;171(5):720-5. Epub 2015 Sep 11. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13653/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26358087 PubMed]
 
−
 
 
−
==CPD {{#subobject:bfa533|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
CPD: '''<u>C</u>'''arfilzomib, '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
<br>KPD: '''<u>K</u>'''yprolis (Carfilzomib), '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen {{#subobject:edd05b|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643003/ Shah et al. 2015]
 
−
|style="background-color:#eeee00"|Phase I (*)
 
−
|-
 
−
|}
 
−
''Note, although this is described as a Phase I trial, an additional 20 patients were enrolled at the MTD, which is the dose reported here. Treatment preceded by [[#CPD|CPD]] x 6.''
 
−
====Chemotherapy====
 
−
*[[Carfilzomib (Kyprolis)]] 27 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 15, 16
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO/IV once per week on days 1, 8, 15, 22
 
−
 
 
−
====Supportive medications====
 
−
*"[[:Category:Antivirals|Anti-viral therapy]]"
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
**[[:Category:Low molecular weight heparins|Low molecular weight heparin]] was used in patients intolerant of aspirin
 
−
 
 
−
'''28-day cycles, given until disease progression, or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
<!-- # '''Abstract:''' Jatin J. Shah, MD, Edward A. Stadtmauer, MD, Rafat Abonour, MD, Adam D. Cohen, MD, William I. Bensinger, MD, Cristina Gasparetto, MD, Jonathan L. Kaufman, MD, Suzanne Lentzsch, MD, Dan T. Vogl, MD, Robert Z. Orlowski, MD, PhD, Erica L. Kim, MPH, Marti McKinley, BSN, MBA, Brian G.M. Durie, MD. A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma. 2013 ASH Annual Meeting abstract 690. [http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/690/ link to abstract] [http://myeloma.org/pdfs/Shah-74-3909.pdf link to presentation] '''contains verified protocol''' -->
 
−
# '''Phase I:''' Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BG. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-90. Epub 2015 Sep 17. [http://www.bloodjournal.org/content/126/20/2284.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643003/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26384354 PubMed]
 
−
 
 
−
==Daratumumab monotherapy {{#subobject:05dc39|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:05fb0a|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1606038 Palumbo et al. 2016 (CASTOR)]
 
−
|style="background-color:#eeee00"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Treatment preceded by [[#DVd_2|DVd]] x 8.''
 
−
====Chemotherapy====
 
−
*[[Daratumumab (Darzalex)]] 16 mg/kg IV once on day 1
 
−
 
 
−
'''28-day cycles until progression'''
 
−
 
 
−
===References===
 
−
<!-- # ASCO 2016 Abstract LBA4 -->
 
−
# Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. [http://www.nejm.org/doi/full/10.1056/NEJMoa1606038 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1606038/suppl_file/nejmoa1606038_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27557302 PubMed]
 
−
 
 
−
==Pomalidomide monotherapy {{#subobject:5d4f4d|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:a3138c|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''ORR'''
 
−
|-
 
−
|[http://www.bloodjournal.org/content/130/10/1198.long Paludo et al. 2017]
 
−
|style="background-color:#eeee00"|Phase I/II
 
−
|86%
 
−
|-
 
−
|}
 
−
''Treatment preceded by [[#PVD|PVD]] x 8.''
 
−
====Chemotherapy====
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
 
 
−
====Supportive medications====
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**Full dose anticoagulation with [[:Category:Low molecular weight heparins|LMWH]] or [[Warfarin (Coumadin)]] could be substituted at physician discretion
 
−
*[[Acyclovir (Zovirax)]] or equivalent for VZV prophylaxis
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Paludo J, Mikhael JR, LaPlant BR, Halvorson AE, Kumar S, Gertz MA, Hayman SR, Buadi FK, Dispenzieri A, Lust JA, Kapoor P, Leung N, Russell SJ, Dingli D, Go RS, Lin Y, Gonsalves WI, Fonseca R, Bergsagel PL, Roy V, Sher T, Chanan-Khan AA, Ailawadhi S, Stewart AK, Reeder CB, Richardson PG, Rajkumar SV, Lacy MQ. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1198-1204. Epub 2017 Jul 6. [http://www.bloodjournal.org/content/130/10/1198.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28684537 PubMed]
 
−
 
 
−
==Pomalidomide & Prednisone {{#subobject:519843|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:171099|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|'''ORR'''
 
−
|-
 
−
|[http://www.bloodjournal.org/content/122/16/2799.full Larocca et al. 2013]
 
−
|style="background-color:#eeee00"|Phase I/II
 
−
|51%
 
−
|-
 
−
|}
 
−
''Details are for the phase II portion of the published phase I/II trial. Treatment preceded by [[#PCP|PCP]] x 6.''
 
−
====Chemotherapy====
 
−
*[[Pomalidomide (Pomalyst)]] 1 mg PO once per day
 
−
*[[Prednisone (Sterapred)]] 25 mg PO once every other day
 
−
 
 
−
====Supportive medications====
 
−
*[[Aspirin]] 100 mg PO once per day or [[:Category:Low_molecular_weight_heparins|low-molecular-weight heparin]] "according to patient risk"
 
−
 
 
−
'''Continuously until any signs of relapse or progression'''
 
−
 
 
−
===References===
 
−
# Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omedé P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A. Pomalidomide, cyclophosphamide and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open label study. Blood. 2013 Oct 17;122(16):2799-806. Epub 2013 Aug 16. [http://www.bloodjournal.org/content/122/16/2799.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23954889 PubMed]
 
−
 
 
−
==RVD {{#subobject:fe8a85|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
RVD: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone
 
−
<br>VDR: '''<u>V</u>'''elcade (Bortezomib), '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<br>VRD: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), '''<u>D</u>'''examethasone
 
−
<br>VRd: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''evlimid (Lenalidomide), low-dose '''<u>d</u>'''examethasone
 
−
===Regimen {{#subobject:0c163e|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123434/ Richardson et al. 2014]
 
−
|style="background-color:#eeee00"|Phase II
 
−
|-
 
−
|}
 
−
 
 
−
''Treatment preceded by [[#RVD_4|salvage RVD]].''
 
−
====Chemotherapy====
 
−
*[[Lenalidomide (Revlimid)]] (at previously tolerated dose) PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] (at previously tolerated dose) IV once per day on days 1 & 8
 
−
*[[Dexamethasone (Decadron)]] 10 mg PO once per day on days 1, 2, 8, 9
 
−
 
 
−
====Supportive medications====
 
−
*[[Aspirin]] 81 mg or 325 mg PO once per day
 
−
*[[:Category:Antivirals|Antiviral]] therapy for VZV prophylaxis
 
−
 
 
−
'''21-day cycles until progression or intolerance'''
 
−
 
 
−
===References===
 
−
# Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase II trial of lenalidomide, bortezomib and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. Epub 2014 Jan 15. [http://www.bloodjournal.org/content/123/10/1461.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123434/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24429336 PubMed]
 
−
 
 
−
=Investigational agents=
 
−
''These are drugs under study with at least some promising results for this disease.''
 
−
 
 
−
*[[Afuresertib (GSK2110183)]]
 
−
*[[Dinaciclib (SCH 727965)]]
 
−
*[[Perifosine (KRX-0401)]]
 
−
*[[Ricolinostat (ACY-1215, Rocilinostat)]]
 
  
 
=Response criteria=
 
=Response criteria=
−
*[http://www.nature.com/leu/journal/v20/n9/full/2404284a.html IMWG international uniform response criteria for multiple myeloma. (Durie et al. Leukemia 2006)] [https://www.ncbi.nlm.nih.gov/pubmed/16855634 PubMed]
+
*[https://doi.org/10.1038/sj.leu.2404284 IMWG international uniform response criteria for multiple myeloma. (Durie et al. Leukemia 2006)] [https://pubmed.ncbi.nlm.nih.gov/16855634/ PubMed]
−
**[http://www.nature.com/leu/journal/v21/n5/full/2404582a.html Make note of these errors] which remain in the online version of the IMWG criteria as of 7/7/2013.
+
**[https://doi.org/10.1038/sj.leu.2404284 Make note of these errors] which remain in the online version of the IMWG criteria as of 7/7/2013.
−
**[http://www.nature.com/leu/journal/v29/n12/full/leu2015290a.html Clarification of the definition of complete response in multiple myeloma (Leukemia 2015)] [https://www.ncbi.nlm.nih.gov/pubmed/26487274 PubMed]
+
**[https://doi.org/10.1038/leu.2015.290 Clarification of the definition of complete response in multiple myeloma (Leukemia 2015)] [https://pubmed.ncbi.nlm.nih.gov/26487274/ PubMed]
−
*[http://www.nature.com/leu/journal/v20/n9/fig_tab/2404284t6.html#figure-title Disease progression criteria (Durie et al. Leukemia 2006)].
+
*[https://doi.org/10.1046/j.1365-2141.1998.00930.x European Blood and Marrow Transplant (EBMT) criteria. (Bladé et al. Br J Hematol 1998)] [https://pubmed.ncbi.nlm.nih.gov/9753033/ PubMed]
−
*[http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.1998.00930.x/full European Blood and Marrow Transplant (EBMT) criteria. (Bladé et al. Br J Hematol 1998)] [https://www.ncbi.nlm.nih.gov/pubmed/9753033 PubMed]
 
  
 
=Prognosis=
 
=Prognosis=
  
 
==[http://myeloma.org/pdfs/Durie-SalmonSS.pdf Durie-Salmon Staging System] - 1975==
 
==[http://myeloma.org/pdfs/Durie-SalmonSS.pdf Durie-Salmon Staging System] - 1975==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Composed of four factors with a modifier based on renal function===
 
===Composed of four factors with a modifier based on renal function===
 
*Serum levels of monoclonal protein (only defined for IgM, IgA, and Bence-Jones)
 
*Serum levels of monoclonal protein (only defined for IgM, IgA, and Bence-Jones)
Line 8,186: Line 104:
  
 
===References===
 
===References===
−
#Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842-54. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197509)36:3%3C842::AID-CNCR2820360303%3E3.0.CO;2-U/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1182674 PubMed]
+
#Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842-54. [https://doi.org/10.1002/1097-0142(197509)36:3%3C842::AID-CNCR2820360303%3E3.0.CO;2-U link to original article] [https://pubmed.ncbi.nlm.nih.gov/1182674/ PubMed]
  
 
==[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T3/ International Staging System (ISS)] - 2005==
 
==[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T3/ International Staging System (ISS)] - 2005==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Composed of two factors===
 
===Composed of two factors===
 
*Serum albumin level
 
*Serum albumin level
Line 8,200: Line 115:
 
*'''Stage I:''' ''Median survival of 62 months''
 
*'''Stage I:''' ''Median survival of 62 months''
 
**Beta-2 microglobulin less than 3.5 mg/l  
 
**Beta-2 microglobulin less than 3.5 mg/l  
−
**Albumin less than or equal to 3.5 g/dl
+
**Albumin greater than or equal to 3.5 g/dl
 
*'''Stage II:''' ''Median survival of 44 months''
 
*'''Stage II:''' ''Median survival of 44 months''
 
**Not meeting stage I or stage III criteria
 
**Not meeting stage I or stage III criteria
Line 8,207: Line 122:
  
 
===References===
 
===References===
−
# Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20;23(15):3412-20. Epub 2005 Apr 4. [http://jco.ascopubs.org/content/23/15/3412.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15809451 PubMed]
+
# Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20;23(15):3412-20. Epub 2005 Apr 4. [https://doi.org/10.1200/jco.2005.04.242 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15809451/ PubMed]
−
# Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. Epub 2008 Oct 30. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18971951 PubMed]
+
# Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. Epub 2008 Oct 30. [https://doi.org/10.1038/leu.2008.291 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18971951/ PubMed]
  
 
==IMWG consensus on risk stratification - 2013==
 
==IMWG consensus on risk stratification - 2013==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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===Composed of four factors===
 
===Composed of four factors===
 
*Serum albumin level
 
*Serum albumin level
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===References===
 
===References===
−
# Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, Miguel JS, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H; International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014 Feb;28(2):269-77. Epub 2013 Aug 26. Review. [http://www.nature.com/leu/journal/v28/n2/full/leu2013247a.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23974982 PubMed]
+
# Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, San Miguel J, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H; International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014 Feb;28(2):269-77. Epub 2013 Aug 26. [https://doi.org/10.1038/leu.2013.247 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23974982/ PubMed]
 +
 
 +
==[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846284/ Revised International Staging System (R-ISS)] - 2015==
  
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==[https://www.ncbi.nlm.nih.gov/pubmed/26240224 Revised International Staging System (R-ISS)] - 2015==
 
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{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
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|[[#top|back to top]]
 
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===Composed of four factors===
 
===Composed of four factors===
 
*Serum albumin level
 
*Serum albumin level
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===References===
 
===References===
−
# Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3. [http://jco.ascopubs.org/content/33/26/2863.full link to original article]
+
# Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3. [https://doi.org/10.1200/jco.2015.61.2267 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846284/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26240224/ PubMed]
  
 
==Miscellaneous==
 
==Miscellaneous==
−
# Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007 Apr 15;109(8):3489-95. Epub 2007 Jan 5. [http://www.bloodjournal.org/content/109/8/3489.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17209057 PubMed]
+
# Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007 Apr 15;109(8):3489-95. Epub 2007 Jan 5. [https://doi.org/10.1182/blood-2006-08-040410 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17209057/ PubMed]
−
# Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, Royer B, Dib M, Voillat L, Bouscary D, Caillot D, Wetterwald M, Pegourie B, Lepeu G, Corront B, Karlin L, Stoppa AM, Fuzibet JG, Delbrel X, Guilhot F, Kolb B, Decaux O, Lamy T, Garderet L, Allangba O, Lifermann F, Anglaret B, Moreau P, Harousseau JL, Facon T. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myélome experience. J Clin Oncol. 2013 Aug 1;31(22):2806-9. Epub 2013 Jun 24. [http://jco.ascopubs.org/content/31/22/2806.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718879/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23796999 PubMed]
+
# Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, Royer B, Dib M, Voillat L, Bouscary D, Caillot D, Wetterwald M, Pegourie B, Lepeu G, Corront B, Karlin L, Stoppa AM, Fuzibet JG, Delbrel X, Guilhot F, Kolb B, Decaux O, Lamy T, Garderet L, Allangba O, Lifermann F, Anglaret B, Moreau P, Harousseau JL, Facon T. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the Intergroupe Francophone du Myélome experience. J Clin Oncol. 2013 Aug 1;31(22):2806-9. Epub 2013 Jun 24. [https://doi.org/10.1200/jco.2012.46.2598 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718879/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23796999/ PubMed]
  
 
=External links=
 
=External links=
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=References=
 
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[[Category:Multiple myeloma regimens]]
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Latest revision as of 11:59, 6 July 2024

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Section editor
Samuelrubinstein.jpg
 Samuel M. Rubinstein, MD
University of North Carolina
Chapel Hill, NC, USA
LinkedIn

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

Note: due to its size/complexity, the multiple myeloma page has been split into sub-pages:

This page will remain as a consolidated location for guidelines and prognostic information.

  • We have moved How I Treat articles to a dedicated page.


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO/CCO

BSH/UKMF

European Myeloma Network (EMN)

EHA/ESMO

IMWG

NCCN

SITC

Response criteria

Prognosis

Durie-Salmon Staging System - 1975

Composed of four factors with a modifier based on renal function

  • Serum levels of monoclonal protein (only defined for IgM, IgA, and Bence-Jones)
  • Number of lytic bone lesions
  • Hemoglobin
  • Serum calcium level

Risk stratification

  • Stage I: (must meet ALL criteria)
    • Hemoglobin greater than 10 g/dL
    • Calcium normal or less than or equal to 12 mg/dL
    • Skeletal survey with normal bone structure (scale 0) or solitary bone plasmacytoma only
    • Monoclonal protein relatively small (IgG M-spike value less than 5 g/dL OR IgA M-spike value less than 3 g/dL OR urine light chain protein less than 4 g/24 hr)
  • Stage II: not stage I or stage III
  • Stage III: (if meets ANY of the criteria)
    • Hemoglobin less than 8.5 g/dL
    • Calcium greater than 12 mg/dL
    • Skeletal survey with extensive skeletal destruction and major fractures
    • Monoclonal protein relatively large (IgG M-spike value greater than 7 g/dL OR IgA M-spike value greater than 5 g/dL OR urine light chain protein greater than 12 g/24 hr)

Modifier

  • A: relatively normal creatinine (less than 2 mg/dL)
  • B: creatinine greater than or equal to 2 mg/dL

References

  1. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842-54. link to original article PubMed

International Staging System (ISS) - 2005

Composed of two factors

  • Serum albumin level
  • Serum beta-2 microglobulin level

Risk stratification

  • Stage I: Median survival of 62 months
    • Beta-2 microglobulin less than 3.5 mg/l
    • Albumin greater than or equal to 3.5 g/dl
  • Stage II: Median survival of 44 months
    • Not meeting stage I or stage III criteria
  • Stage III: Median survival of 29 months
    • Beta-2 microglobulin greater than or equal to 5.5 mg/l

References

  1. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20;23(15):3412-20. Epub 2005 Apr 4. link to original article PubMed
  2. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. Epub 2008 Oct 30. link to original article link to PMC article PubMed

IMWG consensus on risk stratification - 2013

Composed of four factors

  • Serum albumin level
  • Serum beta-2 microglobulin level
  • Age
  • Chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH)

Risk stratification

  • Low risk: (must meet all criteria) Median survival of greater than 10 years
    • ISS Stage I or II
    • Age less than 55 years
    • Absence of the following: del(17p13), t(4;14), +1q21
  • Standard risk: Median survival of 7 years
    • Not meeting low risk or high risk criteria
  • High risk: (if meets both criteria) Median survival of 2 years
    • ISS Stage II or III
    • Either of the following: del(17p13) or t(4;14)

References

  1. Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, San Miguel J, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H; International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014 Feb;28(2):269-77. Epub 2013 Aug 26. link to original article PubMed

Revised International Staging System (R-ISS) - 2015

Composed of four factors

  • Serum albumin level
  • Serum beta-2 microglobulin level
  • Serum LDH
  • Chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH)

Risk stratification

  • Low risk: 5-year overall survival = 82%
    • Beta-2 microglobulin less than 3.5 mg/l
    • Albumin less than or equal to 3.5 g/dl
    • LDH less than the upper limit of normal range
    • Absence of the following: del(17p), t(4;14), t(14;16)
  • Intermediate risk: 5-year overall survival = 62%
    • Not meeting low risk or high risk criteria
  • High risk: (if meets ANY of the criteria) 5-year overall survival = 40%
    • Beta-2 microglobulin greater than or equal to 5.5 mg/l
    • LDH greater than the upper limit of normal range
    • Any of the following: del(17p), t(4;14), t(14;16)

References

  1. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3. link to original article link to PMC article PubMed

Miscellaneous

  1. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007 Apr 15;109(8):3489-95. Epub 2007 Jan 5. link to original article PubMed
  2. Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, Royer B, Dib M, Voillat L, Bouscary D, Caillot D, Wetterwald M, Pegourie B, Lepeu G, Corront B, Karlin L, Stoppa AM, Fuzibet JG, Delbrel X, Guilhot F, Kolb B, Decaux O, Lamy T, Garderet L, Allangba O, Lifermann F, Anglaret B, Moreau P, Harousseau JL, Facon T. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the Intergroupe Francophone du Myélome experience. J Clin Oncol. 2013 Aug 1;31(22):2806-9. Epub 2013 Jun 24. link to original article link to PMC article PubMed

External links

References

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