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Hematology

Diagnosis and Management of Multiple MyelomaA Review

Educational Objective
To identify the key insights or developments described in this article

1 Credit CME

JAMA

Published Online: February 1, 2022

Review

Article Information and Disclosures

Andrew J. Cowan, MD^1,2,3;

Damian J. Green, MD^1,2,3;

Mary Kwok, MD^3,4;

Sarah Lee, MD^1,2,3;

David G. Coffey, MD⁵;

Leona A. Holmberg, MD, PhD^1,2,3;

Sherilyn Tuazon, MD^2,6;

Ajay K. Gopal, MD^1,2,3;

Edward N. Libby, MD^1,2,3

Author Affiliations

¹Division of Medical Oncology, Department of Medicine, University of Washington, Seattle
²Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
³Seattle Cancer Care Alliance, Seattle, Washington
⁴Division of Hematology, Department of Medicine, University of Washington, Seattle
⁵Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida
⁶Now with Bristol Myers Squibb, Seattle, Washington

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Abstract

Importance Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year.

Observations Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β₂ microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization—t(4;14), del(17p), and t(14;16)—to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients.

Conclusions and Relevance Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

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Article Information

Corresponding Author: Edward N. Libby, MD, University of Washington, Department of Internal Medicine, Division of Medical Oncology, 1144 Eastlake Ave E, LG-650, Seattle, Washington 98109 (elibby@seattlecca.org).

Accepted for Publication: January 4, 2022.

Author Contributions: Drs Cowan and Libby had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Cowan, Gopal, Libby.

Acquisition, analysis, or interpretation of data: Cowan, Green, Kwok, Lee, Coffey, Holmberg, Tuazon, Libby.

Drafting of the manuscript: Cowan, Tuazon, Libby.

Critical revision of the manuscript for important intellectual content: All authors.

Supervision: Cowan, Kwok, Gopal, Libby.

Conflict of Interest Disclosures: Dr Cowan reported receiving grants from Janssen, Abbvie, Bristol Myers Squibb, Nektar, Harpoon, and Sanofi and receiving personal fees from Cellectar, Janssen, Abbvie, GlaxoSmithKline, and Secura Bio. Dr Green reported receiving personal fees from Janssen Biotech, Juno Therapeutics, GlaxoSmithKline, Neuleukin Therapeutics, Seattle Genomics, Legend Biotech, Celgene, and Bristol Myers Squibb; receiving clinical trial support from Janssen Biotech, Seattle Genetics, Bristol Myers Squibb, Cellectar Biosciences, and Sanofi-Aventis; receiving grants from Juno Therapeutics and Spring Works Therapeutics; and having a patent 20210171651 pending and holding patent 20200289565, with royalties paid from Juno Therapeutics, a Bristol Myers Squibb Company. Dr Holmberg reported receiving study funding from Seattle Genetics, Sanofi, Millennium-Takada, Bristol Myers Squibb, Merck, and Janssen and holding a patent for Up-To-Date, with royalties paid. Dr Tuazon reported receiving grants from the Conquer Cancer Foundation and National Institutes of Health/National Cancer Institute (P30 CA015704). Dr Gopal reported receiving research funding and study drug from IgM, Agios, Bristol Myers Squibb, and Teva; receiving personal fees from Epizyme, Incyte, Kite, ADC, Karopharm, Nurix, and Cellectar; and receiving consulting fees, research funding, study materials, and/or other personal fees from Merck, Takeda, Gilead, A-Z, Janssen, SeaGen, and Pfizer. Dr Libby reported receiving research funding and study drug from Celgene, Janssen, GlaxoSmithKline, Genentech, BeiGene, and Millenium and receiving consulting fees from Alnylam, Abbvie, Pharmacyclics, Adaptive Biotechnologies, and Akcea. No other disclosures were reported.

Additional Information: Dr Tuazon was employed at the Fred Hutchinson Cancer Research Center for most of the time the manuscript was being developed.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.