Multiple myeloma gammopathies

Targeting Bcl-2 for the treatment of multiple myeloma

Abstract

Despite advances in the treatment of multiple myeloma, the disease still remains incurable for the majority of patients. The overexpression of anti-apoptotic proteins (i.e., Bcl-2, Bcl-XL or Mcl-1) is a hallmark of cancer and favors tumor cell survival and resistance to therapy. The oral drug venetoclax is the first-in-class Bcl-2-specific BH3 mimetic. In myeloma, in vitro sensitivity to venetoclax is mainly observed in plasma cells harboring the t(11;14) translocation, a molecular subgroup associated with high Bcl-2 and low Mcl-1/Bcl-XL expression. In addition with Bcl-2 members expression profile, functional tests as BH3 profiling or in vitro BH3 mimetic drug testing also predict sensitivity to the drug. Phase 1 clinical trials recently confirmed the efficacy of venetoclax monotherapy in heavily pretreated myeloma patients, mostly in patients with t(11;14). In combination with the proteasome inhibitor bortezomib, venetoclax therapy was found to be feasible and allowed promising response rate in relapsed myeloma patients, independent of t(11;14) status. The present review summarizes the current knowledge, “from bench to bedside”, about venetoclax for the treatment of multiple myeloma.

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Author contributions

All authors wrote and critically reviewed the manuscript, and gave final approval. CT, MA and PM are members of Site de Recherche Intégrée sur le Cancer (SIRIC) ILIAD, (INCA-DGOS-Inserm_12558).

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Correspondence to Cyrille Touzeau.

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CT and P Moreau are advisory board member and received honoraria from Abbvie. P Maciag is Abbvie employee and own stock. MA received research funding from Abbvie.

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Touzeau, C., Maciag, P., Amiot, M. et al. Targeting Bcl-2 for the treatment of multiple myeloma. Leukemia 32, 1899–1907 (2018). https://doi.org/10.1038/s41375-018-0223-9

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