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The multiple myelomas — current concepts in cytogenetic classification and therapy

Nature Reviews Clinical Oncology volume 15, pages 409–421 (2018)Cite this article

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Abstract

Multiple myeloma (MM) is a plasma cell neoplasm that accounts for 2% of all haematological malignancies and predominantly affects older individuals (with a median age at diagnosis of 65–70 years). MM is consistently preceded by the clinically recognized precancerous stages monoclonal gammopathy of undetermined significance and smouldering MM. Thus far, MM has been considered as a single disease entity, but the clinical presentation, response to treatment, and survival outcomes of patients with MM are quite heterogeneous and highly dependent on a set of chromosomal abnormalities that can be identified in nearly all of them. These alterations include primary cytogenetic abnormalities, such as translocations involving chromosome 14q and trisomies of odd-numbered chromosomes, as well as secondary abnormalities, such as deletion of chromosome 17p and amplification of chromosome 1q. The aetiology of myeloma is poorly understood, although different nonoverlapping disease entities can be defined on the basis of their specific primary cytogenetic abnormalities, which have a major role in determining clinical behaviour. This classification might enable the development of better treatment strategies focused on the underlying biology of each specific subtype. Herein, we describe treatment approaches that incorporate the current standard of care for patients with MM along with recommended alterations or improvements that might provide additional clinical benefit for certain subgroups of patients.

Key points

  • The multiple myelomas (MM) comprise a group of highly heterogeneous diseases in terms of underlying genetic abnormalities, clinical presentation, and response to treatment and therefore should not be considered as a single malignancy.

  • The precursor states monoclonal gammopathy of undetermined significance and smouldering MM precede MM and are also characterized by the presence of specific clonal cytogenetic alterations.

  • The presence of primary and secondary abnormalities has been incorporated into several risk-stratification systems for MM developed to predict outcomes and to potentially guide treatment approaches.

  • The initial therapy for patients with MM consists of induction with bortezomib, lenalidomide, and dexamethasone followed by autologous stem cell transplantation in eligible patients and then by maintenance therapy with lenalidomide or bortezomib on the basis of cytogenetic risk factors.

  • At relapse, options for therapy have expanded and include daratumumab, elotuzumab, carfilzomib, ixazomib, and panobinostat.

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Fig. 1: Primary and secondary cytogenetic abnormalities in MM.
Fig. 2: Approach to therapy for MM.

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Acknowledgements

S.K.K. and S.V.R. are supported in part by US National Cancer Institute grants CA 107476, CA 168762, and CA186781.

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Nature Reviews Clinical Oncology thanks H. Goldschmidt and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Shaji K. Kumar & S. Vincent Rajkumar

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  1. Shaji K. Kumar
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S.K.K. and S.V.R. both contributed to researching data for the article, discussions of content, writing the manuscript, and editing and reviewing the manuscript before publication.

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Correspondence to Shaji K. Kumar.

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Competing interests

S.K.K. has been a non-paid consultant or advisory board member for AbbVie, Celgene, Janssen, Kite Pharma, Merck, and Takeda and is the Principal Investigator in clinical trials supported by Bristol-Myers Squibb, Celgene, Janssen, Kite Pharma, Roche/Genentech, Sanofi, and Takeda. S.V.R. declares no competing interest.

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Kumar, S.K., Rajkumar, S.V. The multiple myelomas — current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol 15, 409–421 (2018). https://doi.org/10.1038/s41571-018-0018-y

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