Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials.

Relapsed/refractory multiple myeloma (RRMM) remains a challenging condition with a need for more effective treatment options. There are ongoing clinical trials analyzing the effects of anti-B-cell maturation antigen (BCMA) bispecific antibodies (Abs) against RRMM with early, promising results. This study aims to systematically evaluate the safety and efficacy of anti-BCMA bispecific antibodies in patients with RRMM. PubMed, Embase, Web of Science, and the American Society of Hematology (ASH) website were searched for published evidence on the safety and efficacy of anti-BCMA bispecific Abs. Screening was performed using original clinical trials published in English, RRMM, and anti-BCMA-CD3 bispecific Abs as our inclusion criteria. Our search yielded a total of 2211 articles. After screening, we found 11 relevant clinical trials (five phase I, one phase I/II, two phase Ib, two phase II, one phase III). Across the trials, 910 patients with ages ranging from 32 to 82 years were analyzed. A majority of patients were exposed to and/or refractory to triple-class and penta-drugs (prior therapies ranged from 1 to 25). AMG-420, AMG-701, elranatamab, REGN5458, teclistamab (Tec), alnuctamab (ALNUC), and ABBV-383 are the seven anti-BCMA-CD3 bispecific Abs currently being assessed in clinical trials as monotherapy and in combination with immunomodulators/proteasome inhibitors against RRMM. Across the included trials, elranatamab demonstrated overall response rates (ORRs) of 61-64%, while teclistamab ranged from 40% to 78% depending on the regimen. ALNUC and ABBV-383 achieved ORRs of 51% and 57%, respectively. Among patients previously exposed to and/or refractory to anti-BCMA therapies (including antibody-drug conjugates and CAR-T cell therapy), ORRs were 54% for elranatamab and 40% for teclistamab. Incidence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was low with subcutaneous (SC) administration of tec, elranatamab, and ALNUC. Across the studies, no death was reported due to CRS, although it led to treatment discontinuation in one patient in AMG-420, two patients in AMG-701, and dose reduction in three patients in ABBV-383 trials. Our analysis of the trials revealed that bispecific Abs showed efficacy in RRMM, with CRS and hematologic toxicities being the most common adverse events, mostly low-grade and manageable. Based on the promising efficacy and safety of BCMA targeting bispecific Abs, these drugs are emerging as a new therapeutic option for patients with advanced and RRMM.