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Multiple myeloma

Abstract

Multiple myeloma is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. The diagnosis of multiple myeloma is made when clear end-organ damage attributable to the plasma cell proliferative disorder or when findings that suggest a high likelihood of their development are present. Distinguishing symptomatic multiple myeloma that requires treatment from the precursor stages of monoclonal gammopathy of undetermined significance and smouldering multiple myeloma is important, as observation is the standard for those conditions. Much progress has been made over the past decade in the understanding of disease biology and individualized treatment approaches. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have joined the traditional armamentarium (corticosteroids, alkylating agents and anthracyclines) and, along with high-dose therapy and autologous haemopoietic stem cell transplantation, have led to deeper and durable clinical responses. Indeed, an increasing proportion of patients are achieving lasting remissions, raising the possibility of cure for this disease. Success will probably depend on using combinations of effective agents and treating patients in the early stages of disease, such as patients with smouldering multiple myeloma.

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Figure 1: The development of monoclonal gammopathies.
Figure 2: Incidence of multiple myeloma in 2012.
Figure 3: Signalling pathways affected in multiple myeloma.
Figure 4: Tumour microenvironment.
Figure 5: Suggested algorithm for the management of multiple myeloma.

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Contributions

Introduction (S.K.K.); Epidemiology (R.A.K.); Mechanisms/pathophysiology (P.S. and M.v.D.); Diagnosis, screening and prevention (M.-V.M.); Management (V.R. and S.K.K.); Quality of life (F.G.); Outlook (K.C.A.); Overview of Primer (S.K.K.).

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Correspondence to Shaji K. Kumar.

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Competing interests

S.K.K. has served as a consultant for Takeda, Amgen, AbbVie, Merck, Janssen and Skyline Dx. K.C.A. is a member of the advisory board for Millennium Pharmaceuticals, Bristol-Myers Squibb and Gilead Sciences, and is a Scientific Founder of OncoPep and C4 Therapeutics. R.A.K. serves on the disease monitoring committees for Celgene, Bristol-Myers Squibb, Onyx Pharmaceuticals (Amgen) and Pharmacyclics. P.S. is an adviser for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda and Skyline Dx, and has received research support from Amgen, Celgene, Janssen and Takeda. F.G. serves as an adviser for Celgene, Takeda, Roche, Seattle Genetics and Amgen, and has received honoraria from Celgene, Janssen, Amgen, Bristol-Myers Squib and Takeda. M.-V.M. is a consultant for Amgen, Celgene, Janssen and Takeda, and has received speaker's fees from Janssen, Celgene, Amgen and Takeda. V.R. and M.v.D. declare no competing interests.

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Kumar, S., Rajkumar, V., Kyle, R. et al. Multiple myeloma. Nat Rev Dis Primers 3, 17046 (2017). https://doi.org/10.1038/nrdp.2017.46

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