Abstract
Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin protein. MM is the second most common haematological malignancy, with an increasing global incidence. It remains incurable because most patients relapse or become refractory to treatments. MM is a genetically complex disease with high heterogeneity that develops as a multistep process, involving acquisition of genetic alterations in the tumour cells and changes in the bone marrow microenvironment. Symptomatic MM is diagnosed using the International Myeloma Working Group criteria as a bone marrow infiltration of ≥10% clonal plasma cells, and the presence of at least one myeloma-defining event, either standard CRAB features (hypercalcaemia, renal failure, anaemia and/or lytic bone lesions) or biomarkers of imminent organ damage. Younger and fit patients are considered eligible for transplant. They receive an induction, followed by consolidation with high-dose melphalan and autologous haematopoietic cell transplantation, and maintenance therapy. In older adults (ineligible for transplant), the combination of daratumumab, lenalidomide and dexamethasone is the preferred option. If relapse occurs and requires further therapy, the choice of therapy will be based on previous treatment and response and now includes immunotherapies, such as bi-specific monoclonal antibodies and chimeric antigen receptor T cell therapy.
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Acknowledgements
The authors are grateful to J. V. Melo (University of Adelaide, Australia) for her critical review of this manuscript.
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Introduction (M.M. and F.M.); Epidemiology (M.M. and F.M.); Mechanisms/pathophysiology (M.M., F.M., N.J.B. and P.N.); Diagnosis, screening and prevention (M.M., F.M. and E.T.); Management (M.M., F.M. and S.M.); Quality of life (M.M., F.M., V.T.M.H. and N.M.); Outlook (M.M. and F.M.).
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F.M. reports honoraria from BMS, Therakos/Mallinckrodt, Sanofi, JAZZ Pharmaceuticals, Gilead, Novartis, AstraZeneca and MSD, all outside the scope of this work. P.N. reports honoraria from Pfizer, BMS, Janssen and Sanofi, and is a consultant/advisory board member for BMS and Janssen. N.J.B. reports honoraria from Amgen, BMS, Sanofi, Pfizer and Janssen, and is a consultant/advisory board member for BMS, Janssen and Pfizer. V.T.M.H. reports honoraria from AbbVie, Amgen, BMS, GSK, Janssen, Sanofi and Takeda. S.M. reports consulting activity and research fundings from Abbvie, Adaptive Biotechnology, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi and Takeda. M.M. reports grants, lecture honoraria and research support from Adaptive Biotechnologies, Amgen, Astellas, BMS-Celgene, GlaxoSmithKline, Janssen, JAZZ Pharmaceuticals, Novartis, Pfizer, Takeda and Sanofi, all outside the scope of this work. The other authors declare no competing interests.
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Malard, F., Neri, P., Bahlis, N.J. et al. Multiple myeloma. Nat Rev Dis Primers 10, 45 (2024). https://doi.org/10.1038/s41572-024-00529-7
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DOI: https://doi.org/10.1038/s41572-024-00529-7
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