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  • Review Article
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Latest advances and current challenges in the treatment of multiple myeloma

Nature Reviews Clinical Oncology volume 9, pages 135–143 (2012)Cite this article

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Abstract

Effectively treating patients with multiple myeloma is challenging. The development of therapeutic regimens over the past decade that incorporate the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has been the cornerstone of improving the outcome of patients with myeloma. Although these treatment regimens have improved patient survival, nearly all patients eventually relapse. Our improved understanding of the biology of the disease and the importance of the microenvironment has translated into ongoing work to help overcome the challenge of relapse. Several classes of agents including next-generation proteasome inhibitors, immunomodulatory agents, selective histone-deacetylase inhibitors, antibody and antitumor immunotherapy approaches are currently undergoing preclinical and clinical evaluation. This Review provides an update on the latest advances in the treatment of multiple myeloma. In particular, we focus on novel therapies including modulating protein homeostasis, kinases inhibitors, targeting accessory cells and cytokines, and immunomodulatory agents. A discussion of the challenges associated with these therapeutic approaches is also presented.

Key Points

  • Despite recent advances, approximately all patients with multiple myeloma eventually relapse

  • Recognizing the importance of the role of the tumor microenvironment has been one of the most important advances in the field

  • Pomalidomide and oral proteasome inhibitors showed promising activity in preclinical studies and are now being evaluated in early clinical trials

  • Antibodies, in particular elotuzumab (an anti-CS 1 antibody), are an important development; inhibitors of histone deacetylases, the phosphoinositide 3-kinase 3-kinase pathway and heat shock protein 90 are also showing promise

  • Methods to augment antitumor immunotherapy of the immune system are being evaluated

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Figure 1: Suggested approach to the treatment of patients with newly-diagnosed multiple myeloma.
Figure 2: Clinical trials of novel agents targeting myeloma cells and their bone-marrow microenvironment.

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Acknowledgements

The authors wish to acknowledge the assistance of Dr. Diana Cirstea, Dana–Farber Cancer Institute for help with preparation of the figures.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02114, MA, USA

    Anuj Mahindra & Noopur Raje

  2. Dana Farber Cancer Institute, 44 Binney Street, Boston, 02115, MA, USA

    Jacob Laubach, Nikhil Munshi, Paul G. Richardson & Kenneth Anderson

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Contributions

A. Mahindra, J. Laubach and K. Anderson researched data for the article, provided substantial contributions to the discussion of content and wrote the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Kenneth Anderson.

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Competing interests

A. Mahindra is on the Advisory Board for Millennium Pharmaceuticals. N. Raje is on the Advisory Board for Amgen, Celgene, Millennium Pharmaceuticals and Novartis, and receives research support from Acetylon Pharmaceuticals. N. Munshi is on the Advisory Board for Celgene, Millennium Pharmaceuticals, Novartis and Onyx Pharmaceuticals. P. G. Richardson is on the Advisory Board for Bristol-Myers Squibb, Celgene, Johnson & Johnson, Millennium Pharmaceuticals and Novartis. K. Anderson is a consultant for Bristol-Myers Squibb, Celgene, Merck, Millennium Pharmaceuticals, Novartis and Onyx Pharmaceuticals, and is a stockholder/director for Acetylon Pharmaceuticals and OncoPep.

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Mahindra, A., Laubach, J., Raje, N. et al. Latest advances and current challenges in the treatment of multiple myeloma. Nat Rev Clin Oncol 9, 135–143 (2012). https://doi.org/10.1038/nrclinonc.2012.15

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