Integrating Immune Therapies for the Treatment of Multiple Myeloma
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Patients with relapsed or refractory multiple myeloma (RRMM) that is refractory to a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 antibody (triple-class refractory MM) have poor outcomes. Recently, 2 classes of T-cell engaging therapies—CAR T-cell therapy and bispecific T-cell engaging antibodies (BsAbs)—have resulted in unprecedented response rates and survival outcomes in these heavily pretreated patients. The most common targets are BCMA and GPRC5D, with other targets in development. The main classes of adverse effects include cytokine release syndrome, neurotoxicity, infections, and cytopenias, as well as adverse effects unique to specific products. As of September 2023, 2 BCMA-targeting CAR-T cell products, 2 BCMA-targeting BsAbs, and 1 GPRC5D-targeting BsAb, are FDA-approved for standard-of-care use in patients with RRMM who received at least 4 prior lines of therapy, including prior treatment with a proteasome inhibitor, an IMiD, and an anti-CD38 antibody. Earlier-line use is under investigation and has shown promising results. Several other investigational CAR-T constructs and bispecific antibodies are in clinical development. As these therapies become more widely used, including in earlier-line setting, efforts to understand optimal sequencing and mitigate toxicities remain critical.
Submitted September 11, 2023; accepted for publication October 24, 2023.
Disclosures: Dr. Sidana has disclosed serving as a consultant or scientific advisor for Janssen, Bristol-Myers Squibb, Magenta Therapeutics, Sanofi, Takeda, and Pfizer; receiving research funding from Novartis, Janssen, Magenta Therapeutics, Allogene Therapeutics, and Bristol-Myers Squibb; and receiving grant/research support from Stanford Cancer Institute/American Cancer Society Pilot Grant 2022 and the Doris Duke Charitable Foundation. Dr. Mikkilineni has disclosed not receiving any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
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