Multiple myeloma

Section editor
	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:

• Induction (transplant eligible and ineligible)
• First-line consolidation and maintenance
• Relapsed/refractory, including subsequent consolidation and maintenance
• Smoldering multiple myeloma

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

• 2019: Mikhael et al. Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline PubMed
• 2018: Anderson et al. Role of bone-modifying agents in multiple myeloma: American Society of Clinical Oncology Clinical Practice Guideline update PubMed
  • 2007: Kyle et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma PubMed
  • 2002: Berenson et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma PubMed

BSH/UKMF

• 2017: Guidelines for the use of imaging in the management of patients with myeloma PubMed
• 2017: Guidelines for screening and management of late and long-term consequences of myeloma and its treatment PubMed
• 2014: Updates to the guidelines for the diagnosis and management of multiple myeloma PubMed
  • 2011: Guidelines for the diagnosis and management of multiple myeloma 2011 PubMed

European Myeloma Network (EMN)

• 2020: Ludwig et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network PubMed
• 2018: Caers et al. European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when PubMed
• 2018: Gay et al. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives PubMed

EHA/ESMO

• 2021: Dimopoulos et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
  • 2017: Moreau et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
  • 2013: Moreau et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
  • 2010: Harousseau & Dreyling. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
  • 2009: Harousseau & Dreyling. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
  • 2008: Harousseau & Dreyling. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
  • 2007: Harousseau. Multiple myeloma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
  • 2005: Harousseau et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of multiple myeloma PubMed

IMWG

• 2021: Moreau et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group PubMed
• 2021: Terpos et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group PubMed

• 2016: Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group PubMed
• 2016: International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment PubMed
• 2014: International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation PubMed
• 2013: International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease PubMed

NCCN

• NCCN Guidelines - Multiple Myeloma
• 2020: Kumar et al. Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology. PubMed
• 2017: Kumar et al. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
• 2016: Anderson et al. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016 PubMed
• 2015: Anderson et al. Multiple Myeloma, Version 2.2016: Clinical Practice Guidelines in Oncology PubMed
• 2011: Anderson et al. Multiple myeloma. PubMed
• 2009: Anderson et al. NCCN clinical practice guidelines in oncology: multiple myeloma. PubMed
• 2007: Anderson et al. Multiple myeloma. Clinical practice guidelines in oncology. PubMed
• 2004: Anderson et al. Multiple myeloma clinical practice guidelines in oncoloqy. PubMed

SITC

• 2020: Shah et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma PubMed

Response criteria

• IMWG international uniform response criteria for multiple myeloma. (Durie et al. Leukemia 2006) PubMed
  • Make note of these errors which remain in the online version of the IMWG criteria as of 7/7/2013.
  • Clarification of the definition of complete response in multiple myeloma (Leukemia 2015) PubMed
• European Blood and Marrow Transplant (EBMT) criteria. (Bladé et al. Br J Hematol 1998) PubMed

Prognosis

Durie-Salmon Staging System - 1975

Composed of four factors with a modifier based on renal function

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

Risk stratification

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

Modifier

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

References

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

• Mayo Clinic mSMART (Stratification for Myeloma And Risk-adapted Therapy)