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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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]].
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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>
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<br>'''Note: due to its size/complexity, the multiple myeloma page has been split into sub-pages:'''
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*[[Multiple_myeloma,_induction|Induction (transplant eligible and ineligible)]]
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*[[Multiple_myeloma,_consolidation_and_maintenance|First-line consolidation and maintenance]]
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*[[Multiple_myeloma,_relapsed-refractory|Relapsed/refractory, including subsequent consolidation and maintenance]]
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*[[Smoldering multiple myeloma]]
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'''This page will remain as a consolidated location for guidelines and prognostic information.
  
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*''We have moved [[How I Treat]] articles to a dedicated page.''
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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<section begin=guidelines />
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=Guidelines=
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'''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.'''
  
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=Untreated (including transplant ineligible)=
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==[https://www.asco.org ASCO]/CCO==
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*'''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]
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*'''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]
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**'''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]
 +
**'''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]
  
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==BDD==
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==[http://www.b-s-h.org.uk/ BSH]/[http://www.ukmf.org.uk/ UKMF]==
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BDD: '''<u>B</u>'''ortezomib, '''<u>D</u>'''oxorubicin, '''<u>D</u>'''examethasone
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*'''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]
  
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===Regimen===
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==[http://myeloma-europe.org.linux9.curanetserver.dk/index.php European Myeloma Network (EMN)]==
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[[Levels of Evidence]]:  
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*'''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]
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<span
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*'''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]
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style="background:#EEEE00;
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*'''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]
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border-style:solid;">Phase II</span>
 
  
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''This is not specifically a first-line regimen but most patients enrolled on the phase II trial were untreated (50 out of 68)''
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==EHA/[https://www.esmo.org/ ESMO]==
 +
*'''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]
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**'''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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*[[Bortezomib (Velcade)]] 1.0 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
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==[http://imwg.myeloma.org/ IMWG]==
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**Patients without grade 3 or 4 toxicity during the first two cycles could have bortezomib dose increased to 1.3 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
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*'''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]
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*[[Doxorubicin (Adriamycin)]] 9 mg/m2 IV once per day on days 1 & 4
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*'''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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**Patients without grade 3 or 4 toxicity during the first two cycles could have number of doxorubicin doses  increased to 9 mg/m2 IV once per day on days 1, 4, 8, 11
 
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*[[Dexamethasone (Decadron)]] 40 mg (route not specified) once per day on days 1, 4, 8, 11
 
  
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'''21-day cycles x up to 8 cycles'''
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*'''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]
 +
*'''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]
 +
*'''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]
 +
*'''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]
  
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===References===
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==NCCN==
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# Ludwig H, Adam Z, Hajek R, Greil R, Tóthová E, Keil F, Autzinger EM, Thaler J, Gisslinger H, Lang A, Egyed M, Womastek I, Zojer N. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol. 2010 Oct 20;28(30):4635-41. doi: 10.1200/JCO.2010.28.1238. Epub 2010 Sep 7. [http://jco.ascopubs.org/content/28/30/4635.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20823423 PubMed]
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*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1445 NCCN Guidelines - Multiple Myeloma]
 +
*'''2020:''' Kumar et al. [https://doi.org/10.6004/Jnccn.2020.0057 Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/33285522/ PubMed]
 +
*'''2017:''' Kumar et al. [https://doi.org/10.6004/jnccn.2017.0023 Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/28188192/ PubMed]
 +
*'''2016:''' Anderson et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6016087/ NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016] [https://pubmed.ncbi.nlm.nih.gov/27059188/ PubMed]
 +
*'''2015:''' Anderson et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4891187/ Multiple Myeloma, Version 2.2016: Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/26553768/ PubMed]
 +
*'''2011:''' Anderson et al. [https://doi.org/10.6004/Jnccn.2011.0095 Multiple myeloma.] [https://pubmed.ncbi.nlm.nih.gov/21975914/ PubMed]
 +
*'''2009:''' Anderson et al. [https://doi.org/10.6004/Jnccn.2009.0061 NCCN clinical practice guidelines in oncology: multiple myeloma.] [https://pubmed.ncbi.nlm.nih.gov/19878637/ PubMed]
 +
*'''2007:''' Anderson et al. [https://doi.org/10.6004/Jnccn.2007.0014 Multiple myeloma. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/17335683/ PubMed]
 +
*'''2004:''' Anderson et al. [https://doi.org/10.6004/Jnccn.2004.0029 Multiple myeloma clinical practice guidelines in oncoloqy.] [https://pubmed.ncbi.nlm.nih.gov/19795598/ PubMed]
  
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==BiRD==
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==SITC==
−
BiRD: '''<u>Bi</u>'''axin, '''<u>R</u>'''evlimid, '''<u>D</u>'''examethasone
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*'''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 />
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<section begin=bottom />
  
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[[Levels of Evidence]]: '''2013'''
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=Response criteria=
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<span
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*[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]
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style="background:#EEEE00;
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**[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.
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**[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]
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border-color:black;
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*[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]
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border-style:solid;">Phase II</span>
 
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&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;'''2010'''
 
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<span
 
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border-style:solid;">Phase II</span>
 
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<span title="Median PFS 48.3 mo. (BiRd) vs. 27.5 mo. (Rd)"
 
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border-style:solid;">Retrospective improved PFS</span>
 
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<span
 
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style="background:#ff0000;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Retrospective increased toxicity</span>
 
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===Regimen===
 
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*[[Clarithromycin (Biaxin)]] 500 mg PO BID on days 2 to 28 of cycle 1; [[Clarithromycin (Biaxin)]] 500 mg PO BID on days 1 to 28 of cycle 2 and thereafter
 
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*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 3 to 21 of cycle 1; [[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 of cycle 2 and thereafter
 
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*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 3, 8, 15, 22 of cycle 1; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22 of cycle 2 and thereafter
 
−
 
 
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'''28-week cycles'''
 
−
 
 
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Supportive medications:
 
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*[[Aspirin]] 81 mg PO once per day
 
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*Omeprazole (Prilosec) 20 mg PO once per day
 
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*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] PO BID, 3 times a week
 
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===References===
 
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# 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://bloodjournal.hematologylibrary.org/content/111/3/1101.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17989313 PubMed]
 
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#  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 protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20645430 PubMed]
 
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# 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://bloodjournal.hematologylibrary.org/content/121/11/1982.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23299315 PubMed]
 
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==CCd==
 
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CCd: '''<u>C</u>'''arfilzomib, '''<u>C</u>'''yclophosphamide, '''<u>d</u>'''examethasone
 
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===Regimen===
 
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Level of Evidence:
 
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<span
 
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style="background:#EEEE00;
 
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border-style:solid;">Phase II</span>
 
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*[[Carfilzomib (Kyprolis)]] 20 mg/m2 IV once per day on days 1 & 2 of cycle 1 and [[Carfilzomib (Kyprolis)]] 36 mg/m2 IV once per day on days 8, 9, 15, 16 of cycle 1; then [[Carfilzomib (Kyprolis)]] 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16 of cycles 2 to 9
 
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*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 PO once per day on days 1, 8, 15
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles x 9 cycles, followed by maintenance therapy:'''
 
−
 
 
−
====Maintenance therapy====
 
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*[[Carfilzomib (Kyprolis)]] 36 mg/m2 IV once per day on days 1, 2, 15, 16
 
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'''28-day cycles, given until progression of disease or unacceptable toxicity'''
 
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−
===References===
 
−
# Palumbo, Antonio; Bringhen, Sara; Villani, Oreste; Siniscalchi, Agostina; Russo, Eleonora; Uccello, Giuseppina; Cerrato, Chiara; Gilestro, Milena; Rossi, Davide; Boccadoro, Mario. Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) for Newly Diagnosed Multiple Myeloma (MM) Patients. ASH Annual Meeting Abstracts 2012 120: 730 [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/730 link to abstract]
 
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==CRd==
 
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CRd: '''<u>C</u>'''arfilzomib, '''<u>R</u>'''evlimid (lenalidomide), (low-dose) '''<u>d</u>'''examethasone
 
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===Regimen===
 
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Level of Evidence:
 
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<span
 
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style="background:#ff0000;
 
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border-style:solid;">Phase II, <20 patients reported</span>
 
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''It is not clear from the abstract when the 20 mg/m2 vs. 36 mg/m2 dose of carfilzomib is used, nor was it clear what doses were used with oral vs. IV dexamethasone.''
 
−
 
 
−
*[[Carfilzomib (Kyprolis)]] 20 or 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 10 or 20 mg IV/PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
 
 
−
'''28-day cycles x 8 cycles; patients who had at least stable disease then received:'''
 
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−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles x 12 cycles'''
 
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−
===References===
 
−
# Korde, Neha; Zingone, Adriana; Kwok, Mary; Manasanch, Elisabet E.; Costello, Rene; Zuchlinski, Diamond; Mulquin, Marcia; Maric, Irina; Calvo, Katherine R; Braylan, Raul C.; Yuan, Constance; Tembhare, Prashant Ramesh; Stetler-Stevenson, Maryalice; Arthur, Diane C; Raffeld, Mark; Xi, Liqiang; Choyke, Peter; Kurdziel, Karen; Lindenberg, Liza; Steinberg, Seth M.; Roschewski, Mark; Landgren, Ola. Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone (CRd) in Newly Diagnosed Multiple Myeloma (MM) Patients ASH Annual Meeting Abstracts 2012 120: 732 [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/732 link to abstract]
 
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==CTD, CTDa==
 
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CTD: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
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<br>CTDa: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone, '''<u>a</u>'''ttenuated
 
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−
===Regimen #1, Morgan et al. 2011 (CTDa, MRC Myeloma IX)===
 
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Level of Evidence:
 
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<span
 
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border-style:solid;">Phase III</span>
 
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''CTDa is intended for elderly or non-transplant-eligible patients''
 
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*[[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
 
−
 
 
−
'''28-day cycles x 6 to 9 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*For the first 12 weeks of treatment, thromboprophylaxis--for example, with [[Warfarin (Coumadin)]] or 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
 
−
 
 
−
===Regimen #2, Morgan et al. 2012 (CTD, MRC Myeloma IX)===
 
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Level of Evidence:
 
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<span
 
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style="background:#00CD00;
 
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border-color:black;
 
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border-style:solid;">Phase III</span>
 
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−
*[[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
 
−
 
 
−
'''21-day cycles x up to 6 cycles'''
 
−
 
 
−
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 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] [http://www.ncbi.nlm.nih.gov/pubmed/18094721 PubMed]
 
−
*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
 
−
 
 
−
===References===
 
−
# 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. doi: 10.1182/blood-2011-02-338665. Epub 2011 Jun 7. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152492/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21652683 PubMed]
 
−
# 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. doi: 10.3324/haematol.2011.043372. Epub 2011 Nov 4. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291601/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22058209 PubMed]
 
  
−
==CVAD==
+
=Prognosis=
−
CVAD: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone
 
  
−
===Regimen, Morgan et al. 2012 (MRC Myeloma IX)===
+
==[http://myeloma.org/pdfs/Durie-SalmonSS.pdf Durie-Salmon Staging System] - 1975==
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
  
−
''The reference paper has unclear wording about the schedule and total number of doses of vincristine and doxorubicin.  Please contact the editors of this site if you are able to provide a clarification.''
+
===Composed of four factors with a modifier based on renal function===
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg PO once per week
+
*Serum levels of monoclonal protein (only defined for IgM, IgA, and Bence-Jones)
−
*[[Vincristine (Oncovin)]] 0.4 mg IV once per day on days 1 to 4
+
*Number of lytic bone lesions
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
+
*Hemoglobin
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 12 to 15
+
*Serum calcium level
  
−
'''21-day cycles x up to 6 cycles'''
+
===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)
  
−
Supportive medications:
+
===Modifier===
−
*Patients in the study were randomized to a bisphosphonate and received one of the following until progression:
+
*'''A:''' relatively normal creatinine (less than 2 mg/dL)
−
**[[Clodronate (Bonefos)|Sodium clodronate (Bonefos)]] 1600 mg PO once per day
+
*'''B:''' creatinine greater than or equal to 2 mg/dL
−
**[[Zoledronic acid (Zometa)]] 4 mg IV once every 21 to 28 days
 
  
 
===References===
 
===References===
−
# 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. doi: 10.3324/haematol.2011.043372. Epub 2011 Nov 4. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291601/ link to original article] '''contains verified protocol'''--see comment above [http://www.ncbi.nlm.nih.gov/pubmed/22058209 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]
−
 
 
−
==CyBorD, CVD, VCD==
 
−
CyBorD: '''<u>Cy</u>'''clophosphamide, '''<u>Bor</u>'''tezomib, '''<u>D</u>'''examethasone
 
−
<br>CVD: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''elcade, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Reeder et al. 2009===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 PO once per day on days 1, 8, 15, 22
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
 
 
−
'''28-day cycles x 4 to 12 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Proton pump inhibitor (PPI)
 
−
*[[Acyclovir (Zovirax)]]
 
−
*Quinolone antibiotic
 
−
*Antifungal mouthwash recommended
 
  
−
===Regimen #2, Kumar et al. 2012 (EVOLUTION/VDC-mod)===
+
==[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T3/ International Staging System (ISS)] - 2005==
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
  
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m2 IV once per day on days 1, 8, 15
+
===Composed of two factors===
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
+
*Serum albumin level
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15
+
*Serum beta-2 microglobulin level
  
−
'''21-day cycles x 8 cycles, then'''
+
===Risk stratification===
−
 
+
*'''Stage I:''' ''Median survival of 62 months''
−
Maintenance therapy:
+
**Beta-2 microglobulin less than 3.5 mg/l
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
+
**Albumin greater than or equal to 3.5 g/dl
−
 
+
*'''Stage II:''' ''Median survival of 44 months''
−
'''42-day cycles x 4 cycles'''
+
**Not meeting stage I or stage III criteria
−
 
+
*'''Stage III: ''' ''Median survival of 29 months''
−
Supportive medications:
+
**Beta-2 microglobulin greater than or equal to 5.5 mg/l
−
*[[Aspirin]] 325 mg PO once per day
 
−
**[[Warfarin (Coumadin)]] or [[Enoxaparin (Lovenox)]] could be used based on physician discretion
 
−
*PCP prophylaxis recommended
 
−
*[[Acyclovir (Zovirax)]] prophylaxis for Herpes zoster recommended
 
−
*Bisphosphonates could be used "as necessary"
 
−
 
 
−
===Regimen #3, Kumar et al. 2012 (EVOLUTION/VDC)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m2 IV once per day on days 1 & 8
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycles x 8 cycles, then'''
 
−
 
 
−
Maintenance therapy:
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''42-day cycles x 4 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**[[Warfarin (Coumadin)]] or [[Enoxaparin (Lovenox)]] could be used based on physician discretion
 
−
*PCP prophylaxis recommended
 
−
*[[Acyclovir (Zovirax)]] prophylaxis for Herpes zoster recommended
 
−
*Bisphosphonates could be used "as necessary"
 
−
 
 
−
===Regimen #4, Reeder et al. 2010 (once per week bortezomib)===
 
−
''This regimen was described in a letter to the editor of Blood.''
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 PO once per day on days 1, 8, 15, 22
 
−
*[[Bortezomib (Velcade)]] 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 during cycles 1 and 2; [[Dexamethasone (Decadron)]] 40 mg PO once per week during cycles 3 and 4.
 
−
 
 
−
'''28-day cycles x 4 cycles'''
 
  
 
===References===
 
===References===
−
# Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VH, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009 Jul;23(7):1337-41. Epub 2009 Feb 19. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711213/?tool=pubmed link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19225538 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]
−
# Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K, Hentz J, Pirooz NA, Piza JG, Tiedemann R, Mikhael JR, Bergsagel PL, Leis JF, Fonseca R, Stewart AK. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010 Apr 22;115(16):3416-7. doi: 10.1182/blood-2010-02-271676. [http://bloodjournal.hematologylibrary.org/content/115/16/3416.long link to original letter] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20413666 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]
−
# Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. [http://bloodjournal.hematologylibrary.org/content/119/19/4375.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22422823 PubMed]
 
−
 
 
−
==DEX (Dexamethasone)==
 
−
'''<u>DEX</u>'''amethasone
 
  
−
===Regimen #1, Facon et al. 2006 (IFM 95-01)===
+
==IMWG consensus on risk stratification - 2013==
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
  
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 for cycles 1 to 2; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycles 3 to 12
+
===Composed of four factors===
 +
*Serum albumin level
 +
*Serum beta-2 microglobulin level
 +
*Age
 +
*Chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH)
  
−
'''6-week cycles x 12 cycles'''
+
===Risk stratification===
−
 
+
*'''Low risk:''' (must meet all criteria) ''Median survival of greater than 10 years''
−
===Regimen #2, Rajkumar et al. 2006===
+
**[[#International_Staging_System_.28ISS.29_-_2005|ISS]] Stage I or II
−
Level of Evidence:
+
**Age less than 55 years
−
<span
+
**Absence of the following: del(17p13), t(4;14), +1q21
−
style="background:#00CD00;
+
*'''Standard risk:''' ''Median survival of 7 years''
−
padding:3px 6px 3px 6px;
+
**Not meeting low risk or high risk criteria
−
border-color:black;
+
*'''High risk: '''(if meets both criteria) ''Median survival of 2 years''
−
border-width:2px;
+
**[[#International_Staging_System_.28ISS.29_-_2005|ISS]] Stage II or III
−
border-style:solid;">Phase III</span>
+
**Either of the following: del(17p13) or t(4;14)
−
 
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 on odd-numbered cycles; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of even-numbered cycles
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen #3, Rajkumar et al. 2008===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of cycles 1 to 4; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycle 5 and thereafter
 
−
 
 
−
'''28-day cycles'''
 
  
 
===References===
 
===References===
−
# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/16365178 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]
−
# 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://bloodjournal.hematologylibrary.org/content/107/4/1292.long link to original paper] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16174762 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''' [http://www.ncbi.nlm.nih.gov/pubmed/18362366 PubMed]
 
  
−
==DEX-IFN==
+
==[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846284/ Revised International Staging System (R-ISS)] - 2015==
−
'''<u>DEX</u>'''amethasone, '''<u>IFN</u>''': Interferon alfa-2b
 
  
−
===Regimen, Facon et al. 2006 (IFM 95-01)===
+
===Composed of four factors===
−
Level of Evidence:
+
*Serum albumin level
−
<span
+
*Serum beta-2 microglobulin level
−
style="background:#00CD00;
+
*Serum LDH
−
padding:3px 6px 3px 6px;
+
*Chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH)
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
  
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 for cycles 1 to 2; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycles 3 to 12
+
===Risk stratification===
−
*[[Interferon alfa-2b (Intron-A)]] 3 million units SC 3 times per week; start with dexamethasone and stop on on day 42 of the last cycle of dexamethasone
+
*'''Low risk:''' ''5-year overall survival = 82%''
−
 
+
**Beta-2 microglobulin less than 3.5 mg/l
−
'''6-week cycles x 12 cycles'''
+
**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===
 
===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://bloodjournal.hematologylibrary.org/content/107/4/1292.long link to original paper] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16174762 PubMed]
+
# 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]
−
 
 
−
==DVD, DVd, VAD doxil==
 
−
DVD: '''<u>D</u>'''oxil, '''<u>V</u>'''incristine, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Hussein et al. 2002===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO/IV once per day on days 1 to 4
 
−
 
 
−
'''4-week cycles x 6 to 8 cycles'''
 
  
−
Supportive medications:
+
==Miscellaneous==
−
*Vitamin B6 200 mg PO once per day to help reduce risk of palmar-plantar erythrodysesthesia (PPE)
+
# 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. [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]
−
===Regimen #2, Rifkin et al. 2006===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 IV over 1 hour once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose per cycle capped at 2 mg) IV over 5 minutes once on day 1
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''4-week cycles, given until maximal response, progression of disease, or unacceptable toxicity'''
 
−
 
 
−
===Regimen #3, Dimopoulos et al. 2003 & Zervas et al. 2007 (VAD doxil)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 IV over 1 hour once on day 1
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4; in cycles 1 & 3, [[Dexamethasone (Decadron)]] 40 mg PO is also given once per day on days 9 to 12, 17 to 20
 
−
 
 
−
'''4-week cycles x 4 cycles'''
 
−
 
 
−
Supportive medications (which were in the cited Segeren et al. 1999 reference):
 
−
*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 BID for "prophylaxis"
 
−
 
 
−
===References===
 
−
# Hussein MA, Wood L, Hsi E, Srkalovic G, Karam M, Elson P, Bukowski RM. A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients. Cancer. 2002 Nov 15;95(10):2160-8. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.10946/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12412170 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. [http://annonc.oxfordjournals.org/content/14/7/1039.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12853344 PubMed]
 
−
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21662/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16404741 PubMed]
 
−
# Zervas K, Mihou D, Katodritou E, Pouli A, Mitsouli CH, Anagnostopoulos A, Delibasi S, Kyrtsonis MC, Anagnostopoulos N, Terpos E, Zikos P, Maniatis A, Dimopoulos MA; Greek Myeloma Study Group. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol. 2007 Aug;18(8):1369-75. [http://annonc.oxfordjournals.org/content/18/8/1369.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17693650 PubMed]
 
−
 
 
−
==MP, M-DEX==
 
−
MP: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone/rednisolone
 
−
<br>M-DEX: '''<u>M</u>'''elphalan, '''<u>DEX</u>'''amethasone
 
−
 
 
−
===Regimen #1, Facon et al. 2006 (IFM 95-01)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
 
 
−
'''6-week cycles x 12 cycles'''
 
−
 
 
−
===Regimen #2, San Miguel et al. 2008, Mateos et al. 2010 (VISTA)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''6-week cycles x 9 cycles'''
 
−
 
 
−
===Regimen #3===
 
−
''Note: Though this regimen is listed in several online references, no primary reference for this exact regimen could be found.''  Specifically, some references cite the Facon et al. 2006 paper for this regimen, but this regimen is not in that paper.  Many additional variations of MP can be found in the Myeloma Trialists' Collaborative Group 1998 Journal of Clinical Oncology paper referenced below.
 
−
*[[Melphalan (Alkeran)]] 0.15 mg/kg PO once daily on days 1 to 7
 
−
*[[Prednisone (Sterapred)]] 20 mg PO TID on days 1 to 7
 
−
 
 
−
'''6-week cycles'''
 
−
 
 
−
===Regimen #4, Facon et al. 2006, Facon et al. 2007 (IFM 95-01, IFM 99-06)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 for cycles 1 to 2; 40 mg PO once per day on days 1 to 4 of cycles 3 to 12
 
−
 
 
−
'''6-week cycles x 12 cycles'''
 
−
 
 
−
===Regimen #5, Hulin et al. 2009 (IFM 01/01)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.2 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
 
 
−
'''6-week cycles x 12 cycles'''
 
−
 
 
−
===Regimen #6, Palumbo et al. 2012 (MM-015)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.18 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles x 9 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 75 to 100 mg PO once per day as thromboprophylaxis
 
−
 
 
−
===Regimen #7, Wijermans et al. 2010 (HOVON 49)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 5
 
−
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day on days 1 to 5
 
−
 
 
−
'''28-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Bisphosphonate use recommended with [[Pamidronate (Aredia)]] or [[Clodronate (Bonefos)]]; "a maximum treatment period of 2 years was recommended in patients without active disease."
 
−
 
 
−
===Regimen #8, Morgan et al. 2011 (MRC Myeloma IX study)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 7 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisolone (Millipred)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles x 6 to 9 cycles'''
 
−
 
 
−
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
 
−
 
 
−
===Regimen #9, Palumbo et al. 2006===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 4 mg/m2 PO once per day on days 1 to 7
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 7
 
−
 
 
−
'''28-day cycles x 6 cycles'''
 
−
 
 
−
===References===
 
−
# Kyle RA. Monoclonal gammopathy and multiple myeloma in the elderly. Baillieres Clin Haematol. 1987 Jun;1(2):533-57. [http://www.ncbi.nlm.nih.gov/pubmed/3322448 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/16/12/3832.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9850028 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 (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://bloodjournal.hematologylibrary.org/content/107/4/1292.long link to original paper] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16174762 PubMed]
 
−
# 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, GIMEMA. 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2806%2968338-4/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16530576 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2961537-2/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17920916 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
# '''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://bloodjournal.hematologylibrary.org/content/112/8/3107.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18505783 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0801479 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18753647 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/27/22/3664.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19451428 PubMed]
 
−
# '''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. [http://jco.ascopubs.org/content/28/13/2259.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20368561 PubMed]
 
−
# 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. doi: 10.1182/blood-2011-02-338665. Epub 2011 Jun 7. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152492/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21652683 PubMed]
 
−
# Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jędrzejczak 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1112704 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22571200 PubMed]
 
−
# 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; Dutch-Belgium Cooperative Group 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. doi: 10.1200/JCO.2009.26.1610. Epub 2010 Jun 1. [http://jco.ascopubs.org/content/28/19/3160.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20516439 PubMed]
 
−
 
 
−
==MPR, MPR-R, MPL==
 
−
MPL: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>L</u>'''enalidomide
 
−
<br>MPR: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>R</u>'''evlimid
 
−
<br>MPR-R: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>R</u>'''evlimid, '''<u>R</u>'''evlimid maintenance
 
−
 
 
−
===Regimen #1, Palumbo et al. 2007 & Palumbo et al. 2012 (MPR-R)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Melphalan (Alkeran)]] 0.18 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles x 9 cycles, then proceed to maintenance therapy'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles, to continue until relapsed or refractory disease'''
 
−
 
 
−
Supportive medications (varies depending on reference):
 
−
*Palumbo et al. 2012: [[Aspirin]] 75 to 100 mg PO once per day as thromboprophylaxis
 
−
*Palumbo et al. 2007: Ciprofloxacin (Cipro) 500 mg PO BID and [[Aspirin]] 100 mg PO once per day
 
−
 
 
−
===Regimen #2, Palumbo et al. 2012 (MM-015)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.18 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles x 9 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 75 to 100 mg PO once per day as thromboprophylaxis
 
−
 
 
−
===References===
 
−
# Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foà R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA--Italian Multiple Myeloma Network. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. Epub 2007 Sep 4. [http://jco.ascopubs.org/content/25/28/4459.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17785703 PubMed]
 
−
# Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jędrzejczak 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1112704 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22571200 PubMed]
 
−
 
 
−
==MPT==
 
−
MPT: '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>T</u>'''halidomide
 
−
 
 
−
===Regimen #1, Facon et al. 2007 (IFM 99-06)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day , increased as tolerated after  to 4 weeks on therapy to maximum dose of 400 mg once per day, given on days 1 to 42
 
−
 
 
−
'''42-day cycles x 12 cycles'''
 
−
 
 
−
===Regimen #2, Palumbo et al. 2006 (GIMEMA)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Melphalan (Alkeran)]] 4 mg/m2 PO once per day on days 1 to 7
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 7
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 28
 
−
 
 
−
Supportive medications:
 
−
*[[Enoxaparin (Lovenox)]] 40 mg SC once per day on days 1 to 28 of cycles 1 to 4
 
−
 
 
−
'''28-day cycles x 6 cycles, then proceed to maintenance therapy'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day until evidence of relapse or refractory disease
 
−
 
 
−
===Regimen #3, Hulin et al. 2009 (IFM 01/01)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Melphalan (Alkeran)]] 0.2 mg/kg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 2 mg/kg PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
 
 
−
'''42-day cycles x 12 cycles'''
 
−
 
 
−
===Regimen #4, Wijermans et al. 2010 (HOVON 49)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 5
 
−
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day on days 1 to 5
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day
 
−
 
 
−
'''28-day cycles x 8 cycles, then'''
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day
 
−
 
 
−
'''28-day course, then'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day until progression
 
−
 
 
−
Supportive medications (for induction & maintenance periods):
 
−
*Bisphosphonate use recommended with [[Pamidronate (Aredia)]] or [[Clodronate (Bonefos)]]; "a maximum treatment period of 2 years was recommended in patients without active disease."
 
−
*Recommended thromboprophylaxis:
 
−
**During induction therapy, low molecular weight heparin use recommended with nadroparin 2,850 units anti-Xa (for patients >90 kg, dose of 5,700 units anti-Xa)
 
−
**During maintenance therapy, "low-dose [[aspirin]] was advised"
 
−
 
 
−
===References===
 
−
# 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, GIMEMA. 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2806%2968338-4/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16530576 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2961537-2/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17920916 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
# '''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://bloodjournal.hematologylibrary.org/content/112/8/3107.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18505783 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/27/22/3664.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19451428 PubMed]
 
−
# 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; Dutch-Belgium Cooperative Group 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. doi: 10.1200/JCO.2009.26.1610. Epub 2010 Jun 1. [http://jco.ascopubs.org/content/28/19/3160.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20516439 PubMed]
 
−
 
 
−
==Rd==
 
−
Rd: '''<u>R</u>'''evlimid, low dose '''<u>d</u>'''examethasone
 
−
 
 
−
===Regimen, Rajkumar et al. 2010 (ECOG E4A03) & Gay et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles, either given x 4 cycles prior to transplant, or given until progression of disease or unacceptable toxicity'''
 
−
 
 
−
Supportive medications (as described in Rajkumar et al. 2010):
 
−
*One of the following bisphosphonates:
 
−
**[[Pamidronate (Aredia)]] 90 mg IV over 2 to 4 hours once every 4 weeks
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV over 15 minutes once every 4 weeks
 
−
*Thromboprophylaxis required
 
−
 
 
−
===References===
 
−
# Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group. 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042271/?tool=pubmed link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19853510 PubMed]
 
−
# 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 verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20645430 PubMed]
 
−
 
 
−
==RD, RevDex==
 
−
RD: '''<u>R</u>'''evlimid, '''<u>D</u>'''examethasone
 
−
<br>RevDex: '''<u>Rev</u>'''limid, '''<u>Dex</u>'''amethasone
 
−
 
 
−
===Regimen #1, Rajkumar et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
Supportive medications:
 
−
*One of the following bisphosphonates:
 
−
**[[Pamidronate (Aredia)]] 90 mg IV over 2 to 4 hours once every 28 days
 
−
**[[Zoledronic acid (Zometa)]] 4 mg IV over 15 minutes once every 28 days
 
−
*"Thromboprophylaxis" aspirin (80 mg or 325 mg per physician discretion) once per day as thrombosis prophylaxis.
 
−
 
 
−
===Regimen #2, Rajkumar et al. 2005===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of cycles 1 to 4; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycle 5 and thereafter
 
−
 
 
−
'''28-day cycles, given until progression of disease or unacceptable toxicity'''
 
−
 
 
−
Supportive medications:
 
−
*Aspirin 80 mg or 325 mg (depending on physician choice) PO once per day for thromboprophylaxis
 
−
 
 
−
===References===
 
−
# Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, Zeldenrust SR, Kumar S, Greipp PR, Fonseca R, Lust JA, Russell SJ, Kyle RA, Witzig TE, Gertz MA. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005 Dec 15;106(13):4050-3. Epub 2005 Aug 23. [http://bloodjournal.hematologylibrary.org/content/106/13/4050.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16118317 PubMed]
 
−
# Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group. 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042271/?tool=pubmed link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19853510 PubMed]
 
−
 
 
−
==RVD, VDR, VRD==
 
−
RVD: '''<u>R</u>'''evlimid, '''<u>V</u>'''elcade, '''<u>D</u>'''examethasone
 
−
<br>VDR: '''<u>V</u>'''elcade, '''<u>D</u>'''examethasone, '''<u>R</u>'''evlimid
 
−
<br>VRD: '''<u>V</u>'''elcade, '''<u>R</u>'''evlimid, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Richardson et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
 
 
−
'''21-day cycles x 4 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 81 mg or 325 mg PO once per day
 
−
*Antiviral therapy, such as [[Acyclovir (Zovirax)]] 400 mg PO once per day
 
−
*Bisphosphonate
 
−
 
 
−
====Maintenance therapy====
 
−
Patients who responded and tolerated therapy could proceed to maintenance therapy at previously tolerated dose with a different schedule:
 
−
*[[Lenalidomide (Revlimid)]] 25 mg (or previously tolerated dose) PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 (or previously tolerated dose) IV once per day on days 1 & 8
 
−
*[[Dexamethasone (Decadron)]] 20 mg (or previously tolerated dose) PO once per day on days 1, 2, 8, 9
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen #2, Kumar et al. 2012 (EVOLUTION)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycles x 8 cycles, then proceed to maintenance therapy'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''42-day cycles x 4 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**[[Warfarin (Coumadin)]] or [[Enoxaparin (Lovenox)]] could be used based on physician discretion
 
−
*PCP prophylaxis recommended
 
−
*[[Acyclovir (Zovirax)]] prophylaxis for Herpes zoster recommended
 
−
*Bisphosphonates could be used "as necessary"
 
−
 
 
−
===References===
 
−
# Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. Epub 2010 Apr 12. [http://bloodjournal.hematologylibrary.org/content/116/5/679.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20385792 PubMed]
 
−
# Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. [http://bloodjournal.hematologylibrary.org/content/119/19/4375.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22422823 PubMed]
 
−
 
 
−
==RVDC, VDCR==
 
−
RVDC: '''<u>R</u>'''evlimid, '''<u>V</u>'''elcade, '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide
 
−
<br>VDCR: '''<u>V</u>'''elcade, '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''evlimid
 
−
 
 
−
===Regimen, Kumar et al. 2012 (EVOLUTION)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Randomized Phase II, >20 per arm</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 14
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 8, 15
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m2 IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycles x 8 cycles, then proceed to maintenance therapy'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''42-day cycles x 4 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
**[[Warfarin (Coumadin)]] or [[Enoxaparin (Lovenox)]] could be used based on physician discretion
 
−
*PCP prophylaxis recommended
 
−
*[[Acyclovir (Zovirax)]] prophylaxis for Herpes zoster recommended
 
−
*Bisphosphonates could be used "as necessary"
 
−
 
 
−
===References===
 
−
# Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. [http://bloodjournal.hematologylibrary.org/content/119/19/4375.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22422823 PubMed]
 
−
 
 
−
==TD==
 
−
TD: '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Rajkumar et al. 2008===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 14 of cycle 1; [[Thalidomide (Thalomid)]] 100 mg PO once per day on days 15 to 28 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 28 of cycle 2 and thereafter
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of cycles 1 to 4; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycle 5 and thereafter
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen #2, Rajkumar et al. 2002 & Rajkumar et al. 2006===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 28
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 on odd-numbered cycles; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of even-numbered cycles
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen #3, Cavo et al. 2010 & Cavo et al. 2012 (GIMEMA)===
 
−
====Induction therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 14 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 15 to 21 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 21 of cycles 2 & 3
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12
 
−
 
 
−
'''21-day cycles x 3 cycles, then proceed to first stem cell transplant'''
 
−
 
 
−
====First stem cell transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2 (route not specified) once on day -2
 
−
*Autologous stem cell rescue
 
−
 
 
−
'''Wait until count recovery, then proceed to thalidomide & dexamethasone therapy'''
 
−
 
 
−
====Thalidomide & dexamethasone therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles for 3 to 6 months, then proceed to second stem cell transplant'''
 
−
 
 
−
====Second stem cell transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2 (route not specified) once on day -2
 
−
*Autologous stem cell rescue
 
−
 
 
−
'''Wait until 3 months after second transplant, then proceed to thalidomide & dexamethasone therapy'''
 
−
 
 
−
====Thalidomide & dexamethasone therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 20 to 23
 
−
 
 
−
'''35-day cycles x 2 cycles, then proceed to dexamethasone maintenance therapy'''
 
−
 
 
−
====Dexamethasone maintenance therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles until progression, relapse, or undue toxicity'''
 
−
 
 
−
Supportive medications:
 
−
*[[Acyclovir (Zovirax)]] prophylaxis recommended
 
−
 
 
−
===Regimen #4, Rosiñol et al. 2012===
 
−
[[Levels of Evidence]]:
 
−
 
 
−
'''2012:'''
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title="PETHEMA/GEM: Median PFS 56.2 mo. (VTD) vs. 28.2 mo. (TD)
 
−
&#10;GIMEMA: 3-year PFS 60% (VTD) vs. 48%  (TD)"
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Decreased PFS</span>
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Decreased toxicity</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 14 of cycle 1; [[Thalidomide (Thalomid)]] 100 mg PO once per day on days 15 to 28 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 28 of cycle 2 and thereafter
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12
 
−
 
 
−
'''28-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Low-molecular weight heparin or [[aspirin]] recommended
 
−
 
 
−
===References===
 
−
# Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. [http://jco.ascopubs.org/content/21/1/16.full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12506164 PubMed]
 
−
# Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol. 2002 Nov 1;20(21):4319-23. [http://jco.ascopubs.org/content/20/21/4319.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12409330 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''' [http://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''' [http://www.ncbi.nlm.nih.gov/pubmed/18362366 PubMed]
 
−
# 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. doi: 10.1016/S0140-6736(10)61424-9. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. [http://www.sciencedirect.com/science/article/pii/S0140673610614249 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21146205 PubMed]
 
−
# 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://bloodjournal.hematologylibrary.org/content/120/1/9.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22498745 PubMed]
 
−
# 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; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) group. 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. [http://bloodjournal.hematologylibrary.org/content/120/8/1589.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22791289 PubMed]
 
−
 
 
−
==VAD (Velcade); PAD==
 
−
VAD: '''<u>V</u>'''elcade, '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone
 
−
<br>PAD: '''<u>P</u>'''S-341, '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Broyl et al. 2010 & Sonneveld et al. 2012 (HOVON-65/GMMG-HD4)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2 IV once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
 
 
−
'''28-day cycles x 3 cycles'''; stem cells collected 4 to 6 weeks after induction therapy
 
−
 
 
−
Supportive medications (described in the appendix of Sonneveld et al. 2012):
 
−
*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 PO per day (did not specify whether taken once per day or as a divided twice per day dose)
 
−
**[[Valacyclovir (Valtrex)]] 1000 mg PO per day (did not specify whether taken once per day or as a divided twice per day dose)
 
−
 
 
−
====Stem-cell transplant====
 
−
High dose melphalan single (HOVON-65) or tandem (GMMG-HD4)
 
−
 
 
−
====Maintenance====
 
−
Bortezomib maintenance x 2 years, starting 4 weeks after last transplant
 
−
 
 
−
===Regimen #2, Oakervee et al. 2005===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
 
−
*[[Doxorubicin (Adriamycin)]] 4.5 to 9 mg/m2 IV once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18 of cycle 1; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycles 2 to 4
 
−
 
 
−
'''21-day cycles x 4 cycles'''
 
−
 
 
−
===References===
 
−
# Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, Agrawal S, Stec J, Schenkein D, Esseltine DL, Cavenagh JD. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05519.x/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15953001 PubMed]
 
−
# Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. Epub 2010 Sep 21. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2810%2970206-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20864405 PubMed]
 
−
# 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. doi: 10.1200/JCO.2011.39.6820. Epub 2012 Jul 16. [http://jco.ascopubs.org/content/30/24/2946.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22802322 PubMed]
 
−
 
 
−
==VAD (Vincristine), VAD-P==
 
−
VAD: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone
 
−
<br>VAD-P: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen #1, Barlogie et al. 1984===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 96 hours on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 96 hours on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
 
 
−
'''Cycle duration not specified; treatment was given "until a maximum reduction in myeloma protein had occurred."  Patients received four additional cycles of therapy beyond their best response.'''
 
−
 
 
−
Supportive medications:
 
−
*[[Cimetidine (Tagamet)]] prophylaxis (dose not specified)
 
−
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] prophylaxis (dose not specified)
 
−
 
 
−
===Regimen #2, Segeren et al. 1999===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV over 30 minutes once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2 IV over 30 minutes once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of odd-numbered cycles only
 
−
 
 
−
'''4-week cycles'''
 
−
 
 
−
Supportive medications:
 
−
*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 BID for "prophylaxis"
 
−
 
 
−
===Regimen #3, Berenson et al. 2002 (SWOG 9210)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
**Poor-risk patients received 6.75 mg/m2/day (total dose 27 mg/m2) in cycle 1, with increase to full dose starting cycle 2 if no undue toxicity
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once per day on days 9, 11, 13, 15, 17, 19
 
−
 
 
−
'''21-day cycles x at least 6 months or until at least 25% regression of disease'''
 
−
 
 
−
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on prednisone maintenance therapy.
 
−
 
 
−
===Regimen #4, Dimopoulos et al. 2003===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV over 30 minutes once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2 IV over 30 minutes once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4; in cycles 1 & 3, [[Dexamethasone (Decadron)]] 40 mg PO is also given once per day on days 9 to 12, 17 to 20
 
−
 
 
−
'''4-week cycles x 4 cycles'''
 
−
 
 
−
Supportive medications (which were in the cited Segeren et al. 1999 reference):
 
−
*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 BID for "prophylaxis"
 
−
 
 
−
===Regimen #5, Rifkin et al. 2006===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 96 hours on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 96 hours on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen #6, Harousseau et al. 2010 (IFM 2005-01)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of cycles 1 & 2; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycles 3 and thereafter
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Pamidronate (Aredia)]] 90 mg or [[Zoledronic acid (Zometa)]] 4 mg IV once every 28 days until first transplant
 
−
*"Antibiotics, antifungal agents, and antiviral prophylaxis in accordance with local practice."
 
−
 
 
−
===Regimen #7, Facon et al. 2007 (IFM 99-06)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles x 2 cycles'''
 
−
 
 
−
''Followed by stem-cell mobilization and RIC transplant, to be completed''
 
−
 
 
−
===Regimen #8, Broyl et al. 2010 & Sonneveld et al. 2012 (HOVON-65/GMMG-HD4)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg IV once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2 IV once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
 
 
−
'''28-day cycles x 3 cycles'''; stem cells collected 4 to 6 weeks after induction therapy
 
−
 
 
−
Supportive medications (described in the appendix of Sonneveld et al. 2012):
 
−
*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 PO per day (did not specify whether taken once per day or as a divided twice per day dose)
 
−
**[[Valacyclovir (Valtrex)]] 1000 mg PO per day (did not specify whether taken once per day or as a divided twice per day dose)
 
−
 
 
−
====Stem-cell transplant====
 
−
High dose melphalan single (HOVON-65) or tandem (GMMG-HD4)
 
−
 
 
−
====Maintenance====
 
−
Thalidomide maintenance x 2 years, starting 4 weeks after last transplant
 
−
 
 
−
===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. [http://www.nejm.org/doi/full/10.1056/NEJM198405243102104#t=article link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/6546971 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.1999.01279.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10233375 PubMed]
 
−
# 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://bloodjournal.hematologylibrary.org/content/99/9/3163.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11964279 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. [http://annonc.oxfordjournals.org/content/14/7/1039.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12853344 PubMed]
 
−
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21662/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16404741 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2961537-2/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17920916 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
# 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 protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20823406 PubMed]
 
−
# Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. Epub 2010 Sep 21. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2810%2970206-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20864405 PubMed]
 
−
# 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. doi: 10.1200/JCO.2011.39.6820. Epub 2012 Jul 16. [http://jco.ascopubs.org/content/30/24/2946.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22802322 PubMed]
 
−
 
 
−
==VAD-P/Q==
 
−
VAD-P/Q: '''<u>Vi</u>'''ncristine, '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone, '''<u>P</u>'''rednisone, '''<u>Q</u>'''uinine
 
−
 
 
−
===Regimen, Berenson et al. 2002 (SWOG 9210)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 2 to 5
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 2 to 5
 
−
**Poor-risk patients received 6.75 mg/m2/day (total dose 27 mg/m2) in cycle 1, with increase to full dose starting cycle 2 if no undue toxicity
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 5
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once per day on days 10, 12, 14, 16, 18, 20
 
−
*[[Quinine (Qualaquin)]] 400 mg PO TID on days 1 to 6
 
−
 
 
−
'''21-day cycles x at least 6 months or until at least 25% regression of disease'''
 
−
 
 
−
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on prednisone maintenance therapy.
 
−
 
 
−
===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://bloodjournal.hematologylibrary.org/content/99/9/3163.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11964279 PubMed]
 
−
 
 
−
==VD (Velcade)==
 
−
VD: '''<u>V</u>'''elcade, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen, Harousseau et al. 2010 (IFM 2005-01)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12 of cycles 1 & 2; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycles 3 & 4
 
−
 
 
−
'''21-day cycles x 4 cycles'''
 
−
 
 
−
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."
 
−
 
 
−
===References===
 
−
# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/20823406 PubMed]
 
−
# 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] [http://www.ncbi.nlm.nih.gov/pubmed/20644101 PubMed]
 
−
 
 
−
==VDD; PAD==
 
−
VDD: '''<u>V</u>'''elcade, '''<u>D</u>'''oxil, '''<u>D</u>'''examethasone
 
−
<br>PAD: '''<u>P</u>'''S-341, liposomal '''<u>A</u>'''driamycin, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Jakubowiak et al. 2009 & Dytfeld et al. 2011===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV once on day 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 of cycle 1; then [[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 of cycles 2 to 6
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Low-molecular weight heparin 40 mg SC once per day or [[Aspirin]] 81 mg PO once per day for DVT prophylaxis
 
−
*[[Acyclovir (Zovirax)]] 400 mg PO BID for Herpes zoster prophylaxis
 
−
 
 
−
===Regimen #2, Palumbo et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV once on day 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18 of cycle 1; then [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycles 2 to 4
 
−
 
 
−
'''21-day cycles x 4 cycles, then proceed to stem cell mobilization & reinfusion'''
 
−
 
 
−
====Stem cell mobilization & reinfusion====
 
−
''Paper did not describe the full details''
 
−
*Stem cell mobilization with [[Cyclophosphamide (Cytoxan)]] 3000 mg/m2 and [[Filgrastim (Neupogen) | G-CSF]] 10 mcg/kg
 
−
*[[Melphalan (Alkeran)]] 100 mg/m2, given twice, then followed by stem-cell reinfusion
 
−
 
 
−
====Consolidation====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
 
 
−
'''28-day cycles x 4 cycles, then proceed to maintenance therapy'''
 
−
 
 
−
====Maintenance====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles, given until relapsed disease'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 100 mg PO once per day during lenalidomide treatment
 
−
*[[Acyclovir (Zovirax)]] recommended during bortezomib therapy
 
−
 
 
−
===References===
 
−
# Jakubowiak AJ, Kendall T, Al-Zoubi A, Khaled Y, Mineishi S, Ahmed A, Campagnaro E, Brozo C, Braun T, Talpaz M, Kaminski MS. Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma. J Clin Oncol. 2009 Oct 20;27(30):5015-22. Epub 2009 Sep 8. [http://jco.ascopubs.org/content/27/30/5015.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19738129 PubMed]
 
−
# Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [http://jco.ascopubs.org/content/28/5/800.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20048187 PubMed]
 
−
# Dytfeld D, Griffith KA, Friedman J, Lebovic D, Harvey C, Kaminski MS, Jakubowiak AJ. Superior overall survival of patients with myeloma achieving very good partial response or better to initial treatment with bortezomib, pegylated liposomal doxorubicin, and dexamethasone, predicted after two cycles by a free light chain- and M-protein-based model: extended follow-up of a phase II trial. Leuk Lymphoma. 2011 Jul;52(7):1271-80. [http://informahealthcare.com/doi/abs/10.3109/10428194.2011.567316 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21699382 PubMed]
 
−
# '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [http://bloodjournal.hematologylibrary.org/content/122/8/1376.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23775712 PubMed]
 
−
 
 
−
==VMP==
 
−
VMP: '''<u>V</u>'''elcade, '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen #1, San Miguel et al. 2008, Mateos et al. 2010 & Palumbo et al. 2010 (VISTA)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11, 22, 25, 29, 32 of cycles 1 to 4; [[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 8, 22, 29 of cycles 5 to 9
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''42-day cycles x 9 cycles'''
 
−
 
 
−
Supportive medication:
 
−
*Bisphosphonate given to patients with myeloma-associated bone disease unless contraindicated (only mentioned in San Miguel et al. 2008)
 
−
 
 
−
===Regimen #2, Palumbo, et al 2010 & Bringhen et al. 2010 (weekly bortezomib)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Post-hoc analysis</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 8, 15, 22
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''35-day cycles x 9 cycles'''
 
−
 
 
−
===Regimen #3, Gasparetto et al. 2010 ("Short-course" bortezomib)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Melphalan (Alkeran)]] 6 mg/m2 PO once per day on days 1 to 7, given at least 1 hour prior to bortezomib
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 7
 
−
 
 
−
'''28-day cycles x up to 6 cycles'''; treatment could be given beyond 6 cycles at investigator discretion
 
−
 
 
−
Supportive medications:
 
−
*Bisphosphonates and [[Acyclovir (Zovirax)]] recommended
 
−
 
 
−
===Regimen #4, Mateos et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11, 22, 25, 29, 32 
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''42-day cycle x 1 cycle, then'''
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22 
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''35-day cycles x 5 cycles, then'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*Only one of the following:
 
−
**[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
**[[Thalidomide (Thalomid)]] 50 mg PO once per day
 
−
 
 
−
'''3-month cycles x up to 3 years'''
 
−
 
 
−
Supportive medications:
 
−
*"Patients with bone disease received bisphosphonates, and prophylactic [[Acyclovir (Zovirax)|aciclovir]] was recommended."
 
−
*Patients receiving thalidomide needed to have thromboprophylaxis with either [[aspirin]] or low molecular weight heparin
 
−
 
 
−
===References===
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0801479 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18753647 PubMed]
 
−
# Gasparetto C, Gockerman JP, Diehl LF, de Castro CM, Moore JO, Long GD, Horwitz ME, Keogh G, Chute JP, Sullivan KM, Neuwirth R, Davis PH, Sutton LM, Anderson RD, Chao NJ, Rizzieri D. "Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma. Biol Blood Marrow Transplant. 2010 Jan;16(1):70-7. Epub 2009 Sep 3. [http://www.sciencedirect.com/science/article/pii/S108387910900398X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19733251 PubMed]
 
−
# '''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. [http://jco.ascopubs.org/content/28/13/2259.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20368561 PubMed]
 
−
# Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. [http://www.sciencedirect.com/science/article/pii/S147020451070187X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20739218 PubMed]
 
−
# Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. [http://bloodjournal.hematologylibrary.org/content/116/23/4745.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20807892 PubMed]
 
−
# Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. doi:10.1200/JCO.2010.29.8216. Epub 2010 Oct 12. [http://jco.ascopubs.org/content/28/34/5101.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20940200 PubMed]
 
−
# Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. doi: 10.1182/blood-2011-05-353995. Epub 2011 Sep 27. [http://bloodjournal.hematologylibrary.org/content/118/22/5759.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21951682 PubMed]
 
−
 
 
−
==VMPT-VT==
 
−
VMPT-VT: '''<u>V</u>'''elcade, '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>T</u>'''halidomide, '''<u>V</u>'''elcade maintenance, '''<u>T</u>'''halidomide maintenance
 
−
 
 
−
===Regimen #1, Palumbo et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11, 22, 25, 29, 32 of cycles 1 to 4; [[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 8, 22, 29 of cycles 5 to 9
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 42
 
−
 
 
−
'''42-day cycles x 9 cycles, then'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once on day 1
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 14
 
−
 
 
−
'''14-day cycles x 2 years or until disease progression or relapse'''
 
−
 
 
−
===Regimen #2, Palumbo et al. 2010, Bringhen et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''This represents a mid-protocol change where cycle length was decreased from 6 to 5 weeks and bortezomib was changed to weekly dosing''
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 8, 15, 22
 
−
*[[Melphalan (Alkeran)]] 9 mg/m2 PO once per day on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 42
 
−
 
 
−
'''35-day cycles x 9 cycles, then'''
 
−
 
 
−
Maintenance therapy:
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once on day 1
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 14
 
−
 
 
−
'''14-day cycles x 2 years or until disease progression or relapse'''
 
−
 
 
−
===References===
 
−
# Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. doi:10.1200/JCO.2010.29.8216. Epub 2010 Oct 12. [http://jco.ascopubs.org/content/28/34/5101.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20940200 PubMed]
 
−
# Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. [http://bloodjournal.hematologylibrary.org/content/116/23/4745.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20807892 PubMed]
 
−
# Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. doi: 10.1182/blood-2011-05-353995. Epub 2011 Sep 27. [http://bloodjournal.hematologylibrary.org/content/118/22/5759.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21951682 PubMed]
 
−
 
 
−
==VTD==
 
−
VTD: '''<u>V</u>'''elcade (bortezomib), '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Cavo et al. 2010 & Cavo et al. 2012 (GIMEMA)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 14 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 15 to 21 of cycle 1; [[Thalidomide (Thalomid)]]200 mg PO once per day on days 1 to 21 of cycles 2 & 3
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
 
 
−
'''21-day cycles x 3 cycles, then proceed to first stem cell transplant'''
 
−
 
 
−
====First stem cell transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2 once on day -2
 
−
*Autologous stem cell rescue
 
−
 
 
−
'''Wait until count recovery, then proceed to thalidomide & dexamethasone therapy'''
 
−
 
 
−
====Thalidomide & dexamethasone therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles for 3 to 6 months, then proceed to second stem cell transplant'''
 
−
 
 
−
====Second stem cell transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2 once on day -2
 
−
*Autologous stem cell rescue
 
−
 
 
−
'''Wait until 3 months after second transplant, then proceed to bortezomib, thalidomide, dexamethasone therapy'''
 
−
 
 
−
====Bortezomib, thalidomide, dexamethasone therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
 
 
−
'''35-day cycles x 2 cycles, then proceed to dexamethasone maintenance therapy'''
 
−
 
 
−
====Dexamethasone maintenance therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles, given until progression, relapse, or undue toxicity'''
 
−
 
 
−
Supportive medications:
 
−
*[[Acyclovir (Zovirax)]] prophylaxis recommended
 
−
 
 
−
===Regimen #2, Kaufman et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Retrospective</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once daily on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once daily on days 1 to 4, 9 to 12
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] prophylaxis to decrease risk of DVTs
 
−
*Prophylactic "treatment with antiviral and antibiotic medications"
 
−
 
 
−
'''21-day cycles x 3-4 cycles'''
 
−
 
 
−
===Regimen #3, Rosiñol et al. 2012 (PETHEMA/GEM)===
 
−
[[Levels of Evidence]]:
 
−
 
 
−
'''2012:'''
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title="PETHEMA/GEM: Median PFS 56.2 mo. (VTD) vs. 28.2 mo. (TD)
 
−
&#10;GIMEMA: 3-year PFS 60% (VTD) vs. 48% (TD)"
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Improved PFS</span>
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Increased toxicity</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 once per day on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 14 of cycle 1; [[Thalidomide (Thalomid)]] 100 mg PO once per day on days 15 to 28 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 28 of cycle 2 and thereafter
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12
 
−
 
 
−
'''28-day cycles x 6 cycles'''
 
−
 
 
−
Supportive Medications:
 
−
*Low molecular weight heparin (LMWH) or [[aspirin]] recommended
 
−
 
 
−
===References===
 
−
# '''Retrospective:''' Kaufman JL, Nooka A, Vrana M, Gleason C, Heffner LT, Lonial S. Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma: a retrospective study. Cancer. 2010 Jul 1;116(13):3143-51. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25143/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20564642 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961424-9/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21146205 PubMed]
 
−
# 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://bloodjournal.hematologylibrary.org/content/120/1/9.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22498745 PubMed]
 
−
# 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; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) group. 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. [http://bloodjournal.hematologylibrary.org/content/120/8/1589.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22791289 PubMed]
 
−
 
 
−
==VTD-PACE==
 
−
VTD-PACE: '''<u>V</u>'''elcade, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinum (cisplatin), '''<u>A</u>'''driamycin (doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide
 
−
 
 
−
===Regimen, Barlogie et al. 2007 (Total Therapy 3)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Prospective</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.0 mg/m2 SC once per day on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day on days 4 to 7
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 4 to 7
 
−
*[[Cisplatin (Platinol)]] 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 4 to 7
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 4 to 7
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 4 to 7
 
−
*[[Etoposide (Vepesid)]] 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 4 to 7
 
−
*Peripheral blood stem cells (PBSC) are usually collected during cycle 1--cycle 2 PBSC collection is done if needed--with a median CD34 count of 29 x 10<sup>6</sup>/kg.  87% of collections yielded at least 20 x 10<sup>6</sup>/kg.
 
−
 
 
−
'''Duration of each cycle not specified; 2 cycles total are given, no more than 8 weeks apart'''
 
−
 
 
−
During the interim period between cycle 1 and cycle 2, as well as after cycle 2 and prior to transplant, this is given once platelets have recovered to at least 50 x 10<sup>9</sup>/L:
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 21
 
−
 
 
−
'''21-day cycles, given between induction cycles and transplant'''
 
−
 
 
−
In other words, the initial therapy consists of: Induction therapy cycle 1, dexamethasone & thalidomide, induction therapy cycle 2, dexamethasone & thalidomide, then transplant.
 
−
 
 
−
Supportive medications, as described in Barlogie et al. 2006, which Barlogie et al. 2007 refers to.  Note: Barlogie et al. 2007 lists an incorrect title for the reference.  See below for the the correct full reference.
 
−
*[[Filgrastim (Neupogen)]] "was administered to support induction and consolidation chemotherapy regimens"
 
−
*"Prophylactic antibiotics, histamine H2 blockers, and recombinant erythropoietin" were given as needed
 
−
*Low molecular weight heparin (LMWH) prophylaxis was used for all patients receiving thalidomide
 
−
 
 
−
====Autologous stem cell transplant====
 
−
''Full details were not provided in Barlogie et al. 2007.  Tandem autologous transplants were done between 2 to 6 months apart.
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2
 
−
 
 
−
During the interim period after transplant 1 and transplant 2, patients receive:
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 21
 
−
 
 
−
'''21-day cycles, given in the time between and after each transplant'''; if platelets <50 x 10<sup>9</sup>/L, proceed to year 1 of maintenance therapy.  Otherwise, if platelets are at least 50 x 10<sup>9</sup>/L, proceed to consolidation therapy.
 
−
 
 
−
====Consolidation therapy====
 
−
''Cycle 1 of consolidation starts 1.5 to 4 months after the last transplant.  Cycle 2 of consolidation starts 2-4 months after cycle 1 of consolidation.''
 
−
*[[Bortezomib (Velcade)]] 1.0 mg/m2 SC once per day on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 4
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
*[[Cisplatin (Platinol)]] 7.5 mg/m2/day (total dose per cycle: 30 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 7.5 mg/m2/day (total dose per cycle: 30 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2/day (total dose per cycle: 1200 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Etoposide (Vepesid)]] 30 mg/m2/day (total dose per cycle: 120 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
 
 
−
'''2 cycles total are given according to the interval specified above, with the interim therapy below used'''
 
−
 
 
−
During the interim period between cycle 1 and cycle 2, as well as after cycle 2 and prior to maintenance therapy, this is given once platelets have recovered to at least 50 x 10<sup>9</sup>/L:
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 21
 
−
 
 
−
'''21-day cycles, given between consolidation cycles and maintenance'''
 
−
 
 
−
In other words, consolidation therapy consists of: Consolidation therapy cycle 1, dexamethasone & thalidomide, consolidation therapy cycle 2, dexamethasone & thalidomide, then maintenance therapy.
 
−
 
 
−
Supportive medications, as described in Barlogie et al. 2006, which Barlogie et al. 2007 refers to.  Note: Barlogie et al. 2007 lists an incorrect title for the reference.  See below for the the correct full reference.
 
−
*[[Filgrastim (Neupogen)]] "was administered to support induction and consolidation chemotherapy regimens"
 
−
*"Prophylactic antibiotics, histamine H2 blockers, and recombinant erythropoietin" were given as needed
 
−
*Low molecular weight heparin (LMWH) prophylaxis was used for all patients receiving thalidomide
 
−
 
 
−
====Maintenance therapy, year 1 - VTD====
 
−
''Year 1 of maintenance therapy starts 1 to 4 months after consolidation cycle 2.''
 
−
*[[Bortezomib (Velcade)]] 1.0 mg/m2 SC once per day on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 28
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 8 to 11
 
−
 
 
−
'''28-day cycles x 1 year''', then proceed to maintenance therapy years 2 to 3
 
−
 
 
−
====Maintenance therapy, years 2 & 3 - TD====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once every other day
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles x 2 years'''
 
−
 
 
−
===References===
 
−
# Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M, Hollmig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006 Mar 9;354(10):1021-30. [http://www.nejm.org/doi/full/10.1056/NEJMoa053583 link to original article] '''supportive medication details''' [http://www.ncbi.nlm.nih.gov/pubmed/16525139 PubMed]
 
−
# Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K, Pineda-Roman M, Cottler-Fox M, Mohiuddin A, Alsayed Y, Tricot G, Bolejack V, Zangari M, Epstein J, Petty N, Steward D, Jenkins B, Gurley J, Sullivan E, Crowley J, Shaughnessy JD Jr. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol. 2007 Jul;138(2):176-85. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2007.06639.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17593024 PubMed]
 
−
# Kapoor P, Ramakrishnan V, Rajkumar SV. Bortezomib combination therapy in multiple myeloma. Semin Hematol. 2012 Jul;49(3):228-42. doi:10.1053/j.seminhematol.2012.04.010. Review. [http://www.seminhematol.org/article/S0037-1963(12)00033-9/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22726546 PubMed]
 
−
 
 
−
==VTP==
 
−
VTP: '''<u>V</u>'''elcade (bortezomib), '''<u>T</u>'''halidomide, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11, 22, 25, 29, 32 
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 15, then [[Thalidomide (Thalomid)]] 100 mg PO once per day on days 16 to 42
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''42-day cycle x 1 cycle, then'''
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22 
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 4
 
−
 
 
−
'''35-day cycles x 5 cycles, then'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*Only one of the following:
 
−
**[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
**[[Thalidomide (Thalomid)]] 50 mg PO once per day
 
−
 
 
−
'''3-month cycles x up to 3 years'''
 
−
 
 
−
Supportive medications:
 
−
*"Patients with bone disease received bisphosphonates, and prophylactic [[Acyclovir (Zovirax)|aciclovir]] was recommended."
 
−
*Patients receiving thalidomide needed to have thromboprophylaxis with either [[aspirin]] or low-molecular-weight heparin
 
−
 
 
−
===References===
 
−
# Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. [http://www.sciencedirect.com/science/article/pii/S147020451070187X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20739218 PubMed]
 
−
 
 
−
=Post-transplant maintenance/consolidation=
 
−
 
 
−
==Bortezomib (Velcade)==
 
−
 
 
−
===Regimen #1, Mellqvist et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''This trial only included bortezomib-naive patients''
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
 
 
−
'''Beginning 3 months after ASCT, 21-day cycles x 2 cycles, then'''
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles x 4 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*"Bisphosphonates were administered according to national guidelines."
 
−
 
 
−
===Regimen #2, Broyl et al. 2010 & Sonneveld et al. 2012 (HOVON-65/GMMG-HD4)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once every two weeks x 2 years, starting 4 weeks after autologous stem cell transplant
 
−
 
 
−
===References===
 
−
# Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. Epub 2010 Sep 21. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2810%2970206-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20864405 PubMed]
 
−
# 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. doi: 10.1200/JCO.2011.39.6820. Epub 2012 Jul 16. [http://jco.ascopubs.org/content/30/24/2946.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22802322 PubMed]
 
−
# Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. doi: 10.1182/blood-2012-11 to 464503. Epub 2013 Apr 24. [http://bloodjournal.hematologylibrary.org/content/121/23/4647.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23616624 PubMed]
 
−
 
 
−
==DCEP==
 
−
DCEP: '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Induction====
 
−
See details under [[#Multiple_myeloma#VD_.28Velcade.29 | VD (velcade)]] or [[#Multiple_myeloma#VAD_.28Vincristine.29.2C_VAD-P | VAD (Vincristine), VAD-P]]
 
−
 
 
−
====Consolidation====
 
−
*[[Dexamethasone (Decadron)]] 40 mg once per day on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Etoposide (Vepesid)]] 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Cisplatin (Platinol)]] 15 mg/m2/day (total dose per cycle: 60 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
 
 
−
'''28-day cycles x 2 cycles'''
 
−
 
 
−
===References===
 
−
# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/20823406 PubMed]
 
−
 
 
−
==Lenalidomide (Revlimid)==
 
−
===Regimen #1, Attal et al. 2012===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Consolidation====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles x 2 cycles, then'''
 
−
 
 
−
====Maintenance therapy====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day x 3 months, then increased to 15 mg PO once per day if tolerated
 
−
 
 
−
'''given until progression of disease or unacceptable toxicity, or patient choice'''
 
−
 
 
−
Supportive medications:
 
−
*"Thromboprophylaxis was not used"
 
−
 
 
−
===Regimen #2, McCarthy et al. 2012===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''Patients started therapy 100 to 120 days after autologous hematopoietic cell transplant (AHCT).''
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day; after 3 months, dose may be increased to 30 mg PO once per day if the patient's ANC remains at least 1000/uL and platelet count is at least 75,000/uL
 
−
**Dose adjustments can be found in the paper's supplementary appendix
 
−
 
 
−
'''given until progression of disease or unacceptable toxicity'''
 
−
 
 
−
Supportive medications:
 
−
*Patients at high risk of deep venous thrombosis (DVT) or pulmonary embolism (PE) received [[aspirin]], low molecular weight heparin, or [[Warfarin (Coumadin)]] unless contraindicated.  High risk patients were defined as people with: history of diabetes, coronary artery disease, "DVT/PE, significant family history, performance status ≥ 2, smoking history, use of oral contraceptives, and[/or] concurrent use of epoetin."
 
−
 
 
−
===Regimen #3, Palumbo et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''See [[#VDD.3B_PAD|First-line regimens: VDD; PAD: Palumbo et al. 2010]] for details about the induction therapy portion of this regimen.''
 
−
 
 
−
====Consolidation====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
 
 
−
'''28-day cycles x 4 cycles, then proceed to maintenance therapy'''
 
−
 
 
−
====Maintenance====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles, given until relapsed disease'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 100 mg PO once per day during lenalidomide treatment
 
−
 
 
−
===References===
 
−
# Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. [http://jco.ascopubs.org/content/28/5/800.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20048187 PubMed]
 
−
# McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. doi: 10.1056/NEJMoa1114083. [http://www.nejm.org/doi/full/10.1056/NEJMoa1114083 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1114083/suppl_file/nejmoa1114083_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22571201 PubMed]
 
−
# Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM Investigators. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1782-91. [http://www.nejm.org/doi/full/10.1056/NEJMoa1114138 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22571202 PubMed]
 
−
# '''Update:''' Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. [http://bloodjournal.hematologylibrary.org/content/122/8/1376.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23775712 PubMed]
 
−
 
 
−
==Prednisone (Sterapred)==
 
−
 
 
−
===Regimen #1, Berenson et al. 2002 (SWOG 9210)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
Preceded by VAD-P or VAD-P/Q
 
−
 
 
−
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on maintenance therapy:
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day until disease progression
 
−
 
 
−
===Regimen #2, Berenson et al. 2002 (SWOG 9210)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
Preceded by VAD-P or VAD-P/Q
 
−
 
 
−
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on maintenance therapy:
 
−
*[[Prednisone (Sterapred)]] 10 mg PO once every other day until disease progression
 
−
 
 
−
===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://bloodjournal.hematologylibrary.org/content/99/9/3163.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11964279 PubMed]
 
−
 
 
−
==Thalidomide (Thalomid)==
 
−
===Regimen #1, Abdelkefi et al. 2007===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once daily x 6 months, starting 3 months after autologous stem cell transplant
 
−
 
 
−
===Regimen #2, Broyl et al. 2010 & Sonneveld et al. 2012 (HOVON-65/GMMG-HD4)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day x 2 years, starting 4 weeks after autologous stem cell transplant
 
−
 
 
−
===References===
 
−
# Abdelkefi A, Ladeb S, Torjman L, Othman TB, Lakhal A, Romdhane NB, Omri HE, Elloumi M, Belaaj H, Jeddi R, Aissaouï L, Ksouri H, Hassen AB, Msadek F, Saad A, Hsaïri M, Boukef K, Amouri A, Louzir H, Dellagi K, Abdeladhim AB; Tunisian Multiple Myeloma Study Group. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood. 2008 Feb 15;111(4):1805-10. Epub 2007 Sep 17. [http://bloodjournal.hematologylibrary.org/content/111/4/1805.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17875806 PubMed]
 
−
# Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. Epub 2010 Sep 21. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2810%2970206-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20864405 PubMed]
 
−
# 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. doi: 10.1200/JCO.2011.39.6820. Epub 2012 Jul 16. [http://jco.ascopubs.org/content/30/24/2946.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22802322 PubMed]
 
−
 
 
−
==Thalidomide & Prednisone==
 
−
 
 
−
===Regimen, Stewart et al. 2013 (NCICCTG Myeloma 10 Trial)===
 
−
[[Levels of Evidence]]:
 
−
 
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title="4-year PFS 14% (Thal/Pred) vs. 32%  (Observation)"
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Improved PFS</span>
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Decreased QOL</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 200 mg PO once per day
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
 
 
−
'''Begin after autologous transplant and give for four years or until disease progression'''
 
−
 
 
−
Supportive Medications:
 
−
*"Bisphosphonates, histamine-2 blockers, and laxatives were recommended"
 
−
*"Anticoagulant and antiplatelet medications were not mandated"
 
−
 
 
−
===References===
 
−
# Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. doi: 10.1182/blood-2012-09-451872. Epub 2013 Jan 7. [http://bloodjournal.hematologylibrary.org/content/121/9/1517.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23297129 PubMed]
 
−
 
 
−
==VTD==
 
−
VTD: '''<u>V</u>'''elcade (bortezomib), '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Cavo et al. 2010 & Cavo et al. 2012 (GIMEMA)===
 
−
[[Levels of Evidence]]:
 
−
 
 
−
'''2012:'''
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title="3-year PFS 60% (VTD) vs. 48%  (TD)"
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Improved PFS</span>
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Increased toxicity</span>
 
−
 
 
−
====Induction therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 14 of cycle 1; [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 15 to 21 of cycle 1; then [[Thalidomide (Thalomid)]] 200 mg PO once per day on days 1 to 21 of cycles 2 & 3
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12
 
−
 
 
−
'''21-day cycles x 3 cycles, then proceed to first stem cell transplant'''
 
−
 
 
−
====First stem cell transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2 once on day -2
 
−
*Autologous stem cell rescue
 
−
 
 
−
'''Wait until count recovery, then proceed to thalidomide & dexamethasone therapy'''
 
−
 
 
−
====Thalidomide & dexamethasone therapy====
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 28
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles for 3 to 6 months, then proceed to second stem cell transplant'''
 
−
 
 
−
====Second stem cell transplant====
 
−
*[[Melphalan (Alkeran)]] 200 mg/m2 once on day -2
 
−
*Autologous stem cell rescue
 
−
 
 
−
'''Wait until 3 months after second transplant, then proceed to bortezomib, thalidomide, dexamethasone therapy'''
 
−
 
 
−
====Bortezomib, thalidomide, dexamethasone therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day on days 1 to 35
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
 
 
−
'''35-day cycles x 2 cycles, then proceed to dexamethasone maintenance therapy'''
 
−
 
 
−
====Dexamethasone maintenance therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''28-day cycles until progression, relapse, or undue toxicity'''
 
−
 
 
−
Supportive medications:
 
−
*[[Acyclovir (Zovirax)]] prophylaxis recommended
 
−
 
 
−
===Regimen #2, Ladetto et al. 2010===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''Patients in Ladetto et al. 2010 had at least a very good partial response (VGPR) after autologous stem cell transplantation.''
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day, increased by 50 mg each week, up to a maximum of 200 mg PO once per day
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18
 
−
 
 
−
'''35-day cycles x 4 cycles'''
 
−
 
 
−
===References===
 
−
# Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, Crippa C, De Rosa L, Pregno P, Grasso M, Liberati AM, Caravita T, Pisani F, Guglielmelli T, Callea V, Musto P, Cangialosi C, Passera R, Boccadoro M, Palumbo A. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010 Apr 20;28(12):2077-84. doi: 10.1200/JCO.2009.23.7172. Epub 2010 Mar 22. [http://jco.ascopubs.org/content/28/12/2077.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20308672 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961424-9/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21146205 PubMed]
 
−
# 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://bloodjournal.hematologylibrary.org/content/120/1/9.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22498745 PubMed]
 
−
 
 
−
=Relapsed/refractory=
 
−
 
 
−
==BD, Bort-Dex==
 
−
BD: '''<u>B</u>'''ortezomib, '''<u>D</u>'''examethasone
 
−
<br>Bort-Dex: '''<u>Bort</u>'''ezomib, '''<u>Dex</u>'''amethasone
 
−
 
 
−
===Regimen #1, Fukushima et al. 2011 (BD)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO/IV once per day on days 1, 2, 8, 9, 15, 16, 22, 23
 
−
 
 
−
'''35-day cycles, to be continued until complete response, progression of disease, or severe adverse events'''
 
−
 
 
−
===Regimen #2, Hjorth et al. 2012; Dimopoulos et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
 
 
−
'''21-day cycles, to be continued until progression or best response, which would then be followed by 1 to 2 additional cycles'''
 
−
 
 
−
Supportive medications:
 
−
*"Antithrombotic prophylaxis and acyclovir prophylaxis were not mandatory according to the study protocol but used routinely in an increasing proportion of participating centers during the study period."
 
−
 
 
−
===References===
 
−
# Fukushima T, Nakamura T, Iwao H, Nakajima A, Miki M, Sato T, Sakai T, Sawaki T, Fujita Y, Tanaka M, Masaki Y, Nakajima H, Motoo Y, Umehara H. Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Anticancer Res. 2011 Jun;31(6):2297-302. [http://ar.iiarjournals.org/content/31/6/2297.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21737655 PubMed]
 
−
# Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, Andersen NF, Andréasson B, Billström R, Carlson K, Carlsson MS, Flogegård M, Forsberg K, Gimsing P, Karlsson T, Linder O, Nahi H, Othzén A, Swedin A; Nordic Myeloma Study Group (NMSG). Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012 Jun;88(6):485-96. doi: 10.1111/j.1600-0609.2012.01775.x. Epub 2012 Mar 30. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22404182 PubMed]
 
−
# Dimopoulos MA, Beksac M, Benboubker L, Roddie H, Allietta N, Broer E, Couturier C, Mazier MA, Angermund R, Facon T. Phase 2 study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma. Haematologica. 2013 Aug;98(8):1264-72. Epub 2013 May 28. [http://www.haematologica.org/content/98/8/1264.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23716559 PubMed]
 
−
 
 
−
==BLD==
 
−
BLD: '''<u>B</u>'''endamustine, '''<u>L</u>'''enalidomide, '''<u>D</u>'''examethasone
 
−
 
 
−
Level of Evidence: '''2012'''
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
===Regimen===
 
−
''This study involved dose escalation.  Dosages listed are the determined maximally tolerated doses (MTD).''
 
−
*[[Bendamustine (Treanda)]] 75 mg/m2 IV once per day on days 1 & 2
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg (no route specified) once per week
 
−
 
 
−
'''28-day cycles x up to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Aspirin]] 325 mg PO once per day
 
−
*"Gastroprotectant" (H2-blocker or PPI)
 
−
 
 
−
===References===
 
−
# Lentzsch S, O'Sullivan A, Kennedy RC, Abbas M, Dai L, Pregja SL, Burt S, Boyiadzis M, Roodman GD, Mapara MY, Agha M, Waas J, Shuai Y, Normolle D, Zonder JA. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood. 2012 May 17;119(20):4608-13. doi: 10.1182/blood-2011-12-395715. Epub 2012 Mar 26. [http://bloodjournal.hematologylibrary.org/content/119/20/4608.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22451423 PubMed]
 
−
 
 
−
==Bortezomib (Velcade)==
 
−
===Regimen #1, Richardson et al. 2003, Richardson et al. 2005, Richardson et al. 2007 (APEX)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''Richardson et al. 2003 only described the first 8 cycles of treatment''
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
 
−
 
 
−
'''21-day cycles x 8 cycles, then'''
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''35-day cycles x 3 cycles'''
 
−
 
 
−
Supportive medications (described in Richardson et al. 2005):
 
−
*Bisphosphonate IV therapy once every 3 to 4 weeks unless contraindicated
 
−
 
 
−
===Regimen #2, Moreau et al. 2011 (Subcutaneous vs. intravenous Bortezomib (Velcade) +/- Dexamethasone)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 SC/IV 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
 
−
**IV injections are 1 mg/mL (3.5 mg bortezomib reconstituted in 3.5 mL NS), given IV push over 3-5 seconds
 
−
*Patients with suboptimal response after cycle 4 (less than complete response (CR), without disease progression) could also receive, in addition to bortezomib: [[Dexamethasone (Decadron)]] 20 mg PO once daily on days 1, 2, 4, 5, 8, 9, 11, 12
 
−
 
 
−
'''21-day cycles x 8 to 10 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Bisphosphonates "according to established guidelines"
 
−
 
 
−
===Regimen #3, Dimopoulos et al. (VANTAGE 088)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
 
−
 
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa030288 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12826635 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa043445 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15958804 PubMed]
 
−
# 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://bloodjournal.hematologylibrary.org/content/110/10/3557.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17690257 PubMed]
 
−
# 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 to 40. Epub 2011 Apr 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70081-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21507715 PubMed]
 
−
# '''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. doi: 10.3324/haematol.2012.067793. Epub 2012 Jun 11. [http://www.haematologica.org/content/97/12/1925.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22689676 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70398-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24055414 PubMed]
 
−
 
 
−
==Bortezomib, Dexamethasone & Panobinostat==
 
−
 
 
−
===Regimen, Richardson et al. 2013 (PANORAMA 2)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
====Phase 1====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV twice per week
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO four times per week (day of and day after bortezomib)
 
−
*[[Panobinostat (LBH589)]] 20mg PO three times per week
 
−
 
 
−
'''2-weeks on, 1-week off x 8 cycles'''
 
−
 
 
−
====Phase 2====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per week on weeks 1, 2, 4, 5
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO twice per week on weeks 1, 2, 4, 5 (day of and day after bortezomib)
 
−
*[[Panobinostat (LBH589)]] 20mg PO three times per week on weeks 1, 2, 4, 5
 
−
 
 
−
'''6-week cycles until progression, death, or excess toxicity'''
 
−
 
 
−
===References===
 
−
# Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. Epub 2013 Aug 15. [http://bloodjournal.hematologylibrary.org/content/122/14/2331.full link to original article] '''Contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23950178 PubMed]
 
−
 
 
−
==Bortezomib & Doxorubicin liposomal==
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
 
−
*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV over at least 1 hour once on day 4, given after bortezomib
 
−
 
−
'''21-day cycles x up to 8 cycles, given until progression of disease, or unacceptable toxicity'''; treatment could be continued beyond 8 cycles if it was tolerated
 
−
 
 
−
Supportive medications:
 
−
*"Bisphosphonates were used according to established guidelines"
 
−
 
 
−
===References===
 
−
# 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. [http://jco.ascopubs.org/content/25/25/3892.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17679727 PubMed]
 
−
 
 
−
==Bortezomib & Vorinostat==
 
−
 
 
−
===Regimen, Dimopoulos et al. (VANTAGE 088)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
 
−
*[[Vorinostat (Zolinza)]] 400 mg PO daily on days 1 to 14
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70398-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24055414 PubMed]
 
−
 
 
−
==Carfilzomib (Kyprolis)==
 
−
 
 
−
Level of Evidence: '''2012'''
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
===Regimen===
 
−
*[[Carfilzomib (Kyprolis)]] 20 mg/m2 (body surface area capped at 2.2 m2) IV over 2 to 10 minutes once per day on days 1 to 2, 8 to 9, 15 to 16 of cycle 1; then on subsequent cycles, [[Carfilzomib (Kyprolis)]] 27 mg/m2 (body surface area capped at 2.2 m2) IV over 2 to 10 minutes once per day on days 1 to 2, 8 to 9, 15 to 16
 
−
**Note: Neither Vij et al. 2012 nor Siegel et al. 2012 specify that carfilzomib is capped at a body surface area of 2.2 m2, but the [[Carfilzomib (Kyprolis)]] package insert specifies that: "The dose is calculated using the patient’s actual body surface area at baseline. Patients with a body surface area greater than 2.2 m2 should receive a dose based upon a body surface area of 2.2 m2. Dose adjustments do not need to be made for weight changes of less than or equal to 20%."
 
−
 
 
−
'''28-week cycles x up to 12 cycles, given until progression of disease or unacceptable toxicity'''
 
−
 
 
−
Supportive medications:
 
−
*[[Dexamethasone (Decadron)]] 4 mg PO/IV before all doses in cycle 1 (Vij et al. 2012 also administered one dose of dexamethasone 4 mg before the first increased dose of carfilzomib 27 mg/m2).  Restart dexamethasone premedication if patients experience infusion reactions: "fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina."
 
−
*"All patients were to receive oral and intravenous fluids before dosing to assure adequate hydration."
 
−
 
 
−
Dose Adjustments:
 
−
*"Carfilzomib was withheld for grade 3 or 4 hematologic or nonhematologic toxicities and resumed at reduced doses of 15 mg/m2 in cycle 1 or 20 mg/m2 in cycle 2 and above on resolution."
 
−
 
 
−
===References===
 
−
# Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012 Jun 14;119(24):5661-70. Epub 2012 May 3. [http://bloodjournal.hematologylibrary.org/content/119/24/5661.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22555973 PubMed]
 
−
# Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Kunkel L, Wear S, Wong AF, Orlowski RZ, Jagannath S. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012 Oct 4;120(14):2817-25. Epub 2012 Jul 25. [http://bloodjournal.hematologylibrary.org/content/120/14/2817.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22833546 PubMed] '''Pivotal trial for accelerated FDA approval'''
 
−
# [http://kyprolis.com/Content/pdf/PrescribingInformation.pdf Carfilzomib (Kyprolis) package insert]
 
−
 
 
−
==DCEP==
 
−
DCEP: '''<u>D</u>'''examethasone, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II, <20 patients reported</span>
 
−
 
 
−
''These limited details are based on the abstract's description only.  Full article was not available for review.''
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV bolus once per day on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Etoposide (Vepesid)]] 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
*[[Cisplatin (Platinol)]] 15 mg/m2/day (total dose per cycle: 60 mg/m2) IV continuous infusion over 4 days on days 1 to 4
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen) | G-CSF]] SC once per day, starting on day 5, to continue until neutrophil recovery
 
−
 
 
−
===References===
 
−
# Dadacaridou M, Papanicolaou X, Maltesas D, Megalakaki C, Patos P, Panteli K, Repousis P, Mitsouli-Mentzikof C. Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or refractory multiple myeloma patients. J BUON. 2007 Jan-Mar;12(1):41 to 4. [http://www.ncbi.nlm.nih.gov/pubmed/17436400 PubMed]
 
−
 
 
−
==Dexamethasone (Decadron)==
 
−
===Regimen, Miguel et al. 2013 (MM-003)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
 
−
 
 
−
'''28-day cycles''', given until disease progression or unacceptable toxicity
 
−
 
 
−
===References===
 
−
# Miguel JS, 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. [http://www.sciencedirect.com/science/article/pii/S1470204513703802 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24007748 PubMed]
 
−
 
 
−
==PCP==
 
−
PCP: '''<u>P</u>'''omalidomide, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen, Larocca et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
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−
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−
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−
border-style:solid;">Phase II</span>
 
−
 
 
−
''Details are for the phase II portion of the published phase I/II trial.''
 
−
 
 
−
*[[Pomalidomide (Pomalyst)]] 2.5 mg PO once per day
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once every other day
 
−
*[[Prednisone (Sterapred)]] 50 mg PO once every other day
 
−
 
 
−
'''28-day cycles x 6 cycles, followed by:'''
 
−
 
 
−
*[[Pomalidomide (Pomalyst)]] 1 mg PO once per day
 
−
*[[Prednisone (Sterapred)]] 25 mg PO once every other day
 
−
 
 
−
'''Continuously until any signs of relapse or progression'''
 
−
 
 
−
Supportive medications:
 
−
*Aspirin 100 mg PO once per day or low-molecular-weight heparin "according to patient risk"
 
−
 
 
−
===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 Aug 16. [Epub ahead of print] [http://bloodjournal.hematologylibrary.org/content/122/16/2799.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23954889 PubMed]
 
−
 
 
−
==PD==
 
−
PD: '''<u>P</u>'''omalidomide, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen #1, Leleu et al. 2013 (IFM 2009-02) & Miguel et al. 2013 (MM-003)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
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−
border-color:black;
 
−
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−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on day 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles''', given until disease progression or unacceptable toxicity
 
−
 
 
−
Supportive medications:
 
−
*Miguel et al. 2013: Thromboprohpylaxis required.  "Choice of thromboprophylaxis and use of myeloid and erythroid growth factors was left to the physician's discretion." 
 
−
*Leleu et al. 2013: Thromboprophylaxis "at the physician's discretion"
 
−
*Leleu et al. 2013: [[Filgrastim (Neupogen) | G-CSF]] allowed beginning with cycle 2 and on
 
−
 
 
−
===Regimen #2, Lacy et al. 2011; Leleu et al. 2013 (IFM 2009-02)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Randomized Phase II, >20 per arm</span>
 
−
 
 
−
*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 28
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on day 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles''', given until disease progression or unacceptable toxicity
 
−
 
 
−
Supportive medications:
 
−
*Lacy et al. 2011: Aspirin 325 mg PO daily; low molecular weight heparin or warfarin could be substituted at physician discretion
 
−
*Leleu et al. 2013: Thromboprophylaxis "at the physician's discretion"
 
−
*Leleu et al. 2013: [[Filgrastim (Neupogen) | G-CSF]] allowed beginning with cycle 2 and on
 
−
 
 
−
===Regimen #3, Lacy et al. 2009; Lacy et al. 2010; Lacy et al. 2011===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Pomalidomide (Pomalyst)]] 2 mg PO once per day on days 1 to 28
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on day 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles''', given until disease progression or unacceptable toxicity
 
−
 
 
−
Supportive medications:
 
−
*Aspirin 325 mg PO daily; low molecular weight heparin or warfarin could be substituted at physician discretion
 
−
 
 
−
===References===
 
−
# Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Kyle RA, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009 Oct 20;27(30):5008-14. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/30/5008.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720894 PubMed]
 
−
# Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV, Buadi F. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010 Nov;24(11):1934-9. Epub 2010 Sep 9. [http://www.nature.com/leu/journal/v24/n11/full/leu2010190a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20827286 PubMed]
 
−
# Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Stewart AK, Laumann K, Mandrekar SJ, Reeder C, Rajkumar SV, Mikhael JR. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011 Sep 15;118(11):2970-5. Epub 2011 Jun 20. [http://bloodjournal.hematologylibrary.org/content/118/11/2970.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21690557 PubMed]
 
−
# Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, Mathiot C, Petillon MO, Macro M, Roussel M, Pegourie B, Kolb B, Stoppa AM, Hennache B, Bréchignac S, Meuleman N, Thielemans B, Garderet L, Royer B, Hulin C, Benboubker L, Decaux O, Escoffre-Barbe M, Michallet M, Caillot D, Fermand JP, Avet-Loiseau H, Facon T. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. 2013 Mar 14;121(11):1968-1975. Epub 2013 Jan 14.  [http://bloodjournal.hematologylibrary.org/content/early/2013/01/14/blood-2012-09-452375.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23319574 PubMed]
 
−
# Miguel JS, 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. [http://www.sciencedirect.com/science/article/pii/S1470204513703802 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24007748 PubMed]
 
−
 
 
−
==RD==
 
−
RD: '''<u>R</u>'''evlimid, '''<u>D</u>'''examethasone
 
−
 
 
−
===Regimen, Dimopoulos et al. 2007; Weber et al. 2007===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of cycles 1 to 4; [[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4 of cycle 5 and thereafter
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa070594 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18032762 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa070596 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18032763 PubMed]
 
−
 
 
−
==Thal-Dex==
 
−
Thal-Dex: '''<u>Thal</u>'''idomide, '''<u>Dex</u>'''amethasone
 
−
 
 
−
===Regimen, Hjorth et al. 2012===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day, increased by 50 mg every 3 weeks to a maximum of 200 mg PO once per day "unless sufficient response was achieved by a lower dose"
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
 
 
−
'''21-day cycles, to be continued until progression or best response, which would then be followed by 1 to 2 additional cycles'''
 
−
 
 
−
Supportive medications:
 
−
*"Antithrombotic prophylaxis and acyclovir prophylaxis were not mandatory according to the study protocol but used routinely in an increasing proportion of participating centers during the study period."
 
−
 
 
−
===References===
 
−
# Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, Andersen NF, Andréasson B, Billström R, Carlson K, Carlsson MS, Flogegård M, Forsberg K, Gimsing P, Karlsson T, Linder O, Nahi H, Othzén A, Swedin A; Nordic Myeloma Study Group (NMSG). Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012 Jun;88(6):485-96. doi: 10.1111/j.1600-0609.2012.01775.x. Epub 2012 Mar 30. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492844/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22404182 PubMed]
 
−
 
 
−
==VMPT==
 
−
VMPT: '''<u>V</u>'''elcade, '''<u>M</u>'''elphalan, '''<u>P</u>'''rednisone, '''<u>T</u>'''halidomide
 
−
 
 
−
===Regimen, Palumbo et al. 2007===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Bortezomib (Velcade)]] 1.0 to 1.3 mg/m2 IV bolus once per day on days 1, 4, 15, 22
 
−
*[[Melphalan (Alkeran)]] 6 mg/m2 PO once per day on days 1 to 5
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 5
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day on days 1 to 35
 
−
 
 
−
'''35-day cycles x 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://bloodjournal.hematologylibrary.org/content/109/7/2767.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17148584 PubMed]
 
−
 
 
−
=Response criteria=
 
−
[http://www.nature.com/leu/journal/v21/n5/full/2404582a.html Make note of these errors] which remain in the online version as of 7/7/2013.
 
−
*[http://www.nature.com/leu/journal/v20/n9/fig_tab/2404284t5.html#figure-title International uniform response criteria (e.g. CR, sCR, VGPR, PR, SD) for multiple myeloma. (Leukemia 2006)].<ref name="Durie2006">Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. Epub 2006 Jul 20. [http://www.nature.com/leu/journal/v20/n9/full/2404284a.html link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16855634 PubMed]</ref>
 
−
*[http://www.nature.com/leu/journal/v20/n9/fig_tab/2404284t6.html#figure-title Disease progression criteria].<ref name="Durie2006"></ref>
 
−
 
 
−
=Staging=
 
−
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T3/ International Staging System (ISS)]<ref>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] [http://www.ncbi.nlm.nih.gov/pubmed/15809451 PubMed]</ref><ref>Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. doi: 10.1038/leu.2008.291. Epub 2008 Oct 30. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18971951 PubMed]</ref>
 
−
*[http://myeloma.org/pdfs/Durie-SalmonSS.pdf Durie-Salmon Staging System]<ref>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://www.ncbi.nlm.nih.gov/pubmed/1182674 PubMed]</ref>
 
  
 
=External links=
 
=External links=
−
*[http://msmart.org/index.html Mayo Clinic mSMART (Stratification for Myeloma And Risk-adapted Therapy)]
+
*[https://www.msmart.org/ Mayo Clinic mSMART (Stratification for Myeloma And Risk-adapted Therapy)]
  
 
=References=
 
=References=
 
<references/>
 
<references/>
 +
<section end=bottom />
 +
 +
[[Category:Null pages]]

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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