Multiple myeloma

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.

Section editor

Samuel M. Rubinstein, MD, MSCI
UNC Chapel Hill
Chapel Hill, NC, USA

Dr. Rubinstein's LinkedIn profile

Related pages

• Sub-pages:
  • Induction for newly diagnosed multiple myeloma (NDMM; transplant eligible and ineligible)
  • Consolidation and maintenance for NDMM
  • Treatment for relapsed/refractory multiple myeloma (RRMM), including subsequent consolidation and maintenance
  • Smoldering multiple myeloma
• MM oral medication dose adjustments
• MM global drug approvals
• How I Treat articles
• Historical regimens for MM
• Placebo or observational studies in MM

Clinical practice guidelines

Given the rapid evolution of evidence in hematology and oncology, any guideline older than five years should be regarded as historical information only.

ASCO/CCO guidelines

• 2026: Hicks et al. Treatment of Multiple Myeloma: ASCO-Ontario Health (Cancer Care Ontario) Living Guideline
• 2019: Mikhael et al. Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline link to EuroPMC abstract
• 2018: Anderson et al. Role of bone-modifying agents in multiple myeloma: American Society of Clinical Oncology Clinical Practice Guideline update link to EuroPMC abstract
  • 2007: Kyle et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma link to EuroPMC abstract
  • 2002: Berenson et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma link to EuroPMC abstract

Myeloma Australia guidelines

• 2022: Quach et al. Clinical Practice Guideline Multiple Myeloma (PDF)

BSH/UKMF guidelines

• 2021: Sive J et al. Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum Guideline link to EuroPMC abstract
• 2017: Chantry A et al. Guidelines for the use of imaging in the management of patients with myeloma link to EuroPMC abstract
• 2017: Snowden JA et al. Guidelines for screening and management of late and long-term consequences of myeloma and its treatment link to EuroPMC abstract
• 2014: Pratt G et al. Updates to the guidelines for the diagnosis and management of multiple myeloma link to EuroPMC abstract
  • 2011: Bird JM et al. Guidelines for the diagnosis and management of multiple myeloma 2011 link to EuroPMC abstract

European Myeloma Network (EMN) guidelines

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

EHA/ESMO guidelines

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

International Myeloma Working Group (IMWG) guidelines

• 2024: Rodriguez-Otero P et al. International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma link to EuroPMC abstract
• 2022: Raje NS et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group link to EuroPMC abstract
• 2021: Terpos et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group link to EuroPMC abstract
  • 2013: International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease free full text available at EuroPMC link to EuroPMC abstract
• 2016: Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group free full text available at EuroPMC link to EuroPMC abstract
• 2016: International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment link to EuroPMC abstract
• 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 free full text available at EuroPMC link to EuroPMC abstract

Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) guidelines

• 2018: Gonsalves et al. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement free full text available at EuroPMC link to EuroPMC abstract
• 2013: Mikhael et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013 link to EuroPMC abstract
  • 2009: Kumar et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines free full text available at EuroPMC link to EuroPMC abstract
  • 2007: Dispenzieri et al. Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement link to EuroPMC abstract

National Comprehensive Cancer Network® (NCCN®) guidelines

NCCN Guidelines - Multiple Myeloma

• 2024: Kumar et al. Multiple Myeloma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology link to EuroPMC abstract
• 2020: Kumar et al. Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology link to EuroPMC abstract
• 2017: Kumar et al. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology link to EuroPMC abstract
• 2016: Anderson et al. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016 free full text available at EuroPMC link to EuroPMC abstract
• 2015: Anderson et al. Multiple Myeloma, Version 2.2016: Clinical Practice Guidelines in Oncology free full text available at EuroPMC link to EuroPMC abstract
• 2011: Anderson et al. Multiple myeloma link to EuroPMC abstract
• 2009: Anderson et al. NCCN clinical practice guidelines in oncology: multiple myeloma link to EuroPMC abstract
• 2007: Anderson et al. Multiple myeloma. Clinical practice guidelines in oncology link to EuroPMC abstract
• 2004: Anderson et al. Multiple myeloma clinical practice guidelines in oncology link to EuroPMC abstract

Society for Immunotherapy of Cancer (SITC) guidelines

• 2020: Shah et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma free full text available at EuroPMC link to EuroPMC abstract

Response criteria

• IMWG international uniform response criteria for multiple myeloma. (Durie et al. Leukemia 2006) link to EuroPMC abstract
  • This article had several errors which remained in the online version of the IMWG criteria as of July 7, 2013.
  • Clarification of the definition of complete response in multiple myeloma (Leukemia 2015) link to EuroPMC abstract
• European Blood and Marrow Transplant (EBMT) criteria. (Bladé et al. Br J Hematol 1998) link to EuroPMC abstract

Prognosis

Durie-Salmon Staging System - 1975

Durie-Salmon is composed of four factors with a modifier based on renal function

Factors

• 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 link to EuroPMC abstract

• link to scoring sheet at Myeloma.org (PDF)

International Staging System (ISS) - 2005

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 link to EuroPMC abstract
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 free full text available at EuroPMC link to EuroPMC abstract

IMWG consensus on risk stratification - 2013

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
  • Younger than 55 years old
  • Absence of these findings: 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 these: 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 link to EuroPMC abstract

IMWG consensus on risk stratification - 2025

Risk stratification

High risk if at least one of these abnormalities present:

• Presence of del(17p), with a cutoff of >20% clonal fraction, and/or TP53 mutation
• An IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32)
• Monoallelic del(1p32) along with 1q+ or biallelic del(1p32)
• β2 microglobulin ≥5.5 mg/L with normal creatinine (<1.2 mg/dL)

References

1. Avet-Loiseau H, Davies FE, Samur MK, Corre J, D'Agostino M, Kaiser MF, Raab MS, Weinhold N, Gutierrez NC, Paiva B, Neri P, Weisel K, Maura F, Walker BA, Bustoros M, Stewart AK, Usmani SZ, Hillengass J, Chng WJ, Keats JJ, Martinez-Lopez J, Sperling AS, Touzeau C, Zhan F, Raje NS, Cavo M, Bolli N, Ghobrial IM, Dhodapkar MV, Jagannath S, Spencer A, Parekh S, Bahlis NJ, Lonial S, Sonneveld P, Bergsagel L, Orlowski RZ, Morgan G, Mateos MV, Rajkumar SV, San Miguel JF, Anderson KC, Moreau P, Kumar S, Prósper F, Munshi NC. International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma. J Clin Oncol. 2025 Aug;43(24):2739-2751. Epub 2025 Jun 9. link to original article link to EuroPMC abstract

Revised International Staging System (R-ISS) - 2015

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 these findings: 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 these: 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 free full text available at EuroPMC link to EuroPMC abstract

Second Revised International Staging System (R2-ISS) - 2022

Factors

• ISS-III: 1.5 points
• ISS-II: 1 point
• del(17p): 1 point
• High LDH: 1 point
• t(4;14): 1 point
• 1q+: 0.5 points

Risk stratification

• Low risk: 0 points
  • Median OS: NYR
  • Median PFS: 68 mo
• Low-intermediate risk: 0.5 to 1 points
  • Median OS: 109.2 mo
  • Median PFS: 45.5 mo
• Intermediate-high risk: 1.5 to 2.5 points
  • Median OS: 68.5 mo
  • Median PFS: 30.2 mo
• High risk: 3 to 5 points
  • Median OS: 37.9 mo
  • Median PFS: 19.9 mo

References

1. D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall'Olio D, van de Donk NWCJ, Jackson G, Rocchi S, Salwender H, Bladé Creixenti J, van der Holt B, Castellani G, Bonello F, Capra A, Mai EK, Dürig J, Gay F, Zweegman S, Cavo M, Kaiser MF, Goldschmidt H, Hernández Rivas JM, Larocca A, Cook G, San-Miguel JF, Boccadoro M, Sonneveld P. Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project. J Clin Oncol. 2022 Oct 10;40(29):3406-3418. Epub 2022 May 23. Erratum in: J Clin Oncol. 2022 Dec 1;40(34):4032. link to original article link to EuroPMC abstract

Miscellaneous

References

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 link to EuroPMC abstract
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 free full text available at EuroPMC link to EuroPMC abstract

Additional resources

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