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Bispecific Antibodies for the Treatment of Multiple Myeloma

  • T-Cell and Other Lymphoproliferative Malignancies (J Zain, Section Editor)
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Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Advances in multiple myeloma therapies have greatly improved outcomes for patients living with the disease, although to date there is yet to be a cure. Cellular and immunotherapies, approved or in development, offer the promise of significantly advancing toward that possibility. The aim of this review is to provide a synopsis and commentary on the current and future states of bispecific agents aimed at harnessing the antineoplastic potential of T-cells in treating and eradicating myeloma.

Recent Findings

Numerous bispecific agents are in clinical development with some on the precipice of regulatory approval. While BCMA remains the principal target, some agents are directed at novel targets such as GPRC5D and FcRH5. The constructs vary in design and pharmacokinetics which has dosing and administration implications. The toxicity profiles of these agents generally reflect that of other immune therapies, including cytokine release syndrome and rarely neurotoxicity, although immunosuppression has also led to elevated infection risks. However, the toxicities are generally manageable and offset by unprecedented efficacy seen in such heavily pretreated cohorts.

Summary

Bispecific agents are poised to significantly alter the treatment paradigms for myeloma. They provide a convenient “off-the-shelf” platform with often deep and durable responses. Toxicities are often limited in duration and severity. In the early-phase trials, many patients have been able to remain on treatment for extended periods, even among those with high-risk features. Upcoming trials are likely to explore earlier implementation of these agents in order to offer this therapeutic opportunity to broader cohorts.

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Authors and Affiliations

  1. Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd, Duarte, CA, 91010, USA

    Scott R. Goldsmith & Shawn Streeter

  2. Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Fahrettin Covut

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Correspondence to Scott R. Goldsmith.

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SRG has consulted for Janssen Pharmaceuticals, Sanofi-Genzyme, Wugen Inc., and Oncovalent Theapeutics, and received travel funding from Adaptive Biosciences. SS and FC declare no conflicts of interest.

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Goldsmith, S.R., Streeter, S. & Covut, F. Bispecific Antibodies for the Treatment of Multiple Myeloma. Curr Hematol Malig Rep 17, 286–297 (2022). https://doi.org/10.1007/s11899-022-00675-3

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