BCMA versus GPRC5D bispecific antibodies in relapsed/refractory multiple myeloma: A systematic review and meta‐analysis guiding treatment selection

Bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA) or G protein-coupled receptor, class C, group 5, member D (GPRC5D) represent effective options for relapsed or refractory multiple myeloma (RRMM), yet direct comparative evidence remains limited. We performed a systematic review and meta-analysis of studies evaluating BCMA- or GPRC5D-targeted BsAbs in RRMM. Thirty studies comprising 3218 patients were included. Random-effects models were used to pool efficacy and safety outcomes, followed by meta-regression to identify study-level moderators of response. At the recommended phase 2 dose, BCMA- and GPRC5D-targeted BsAbs showed comparable efficacy, with overall response rates (ORRs) of 65% (95% confidence interval [CI], 60%-70%) and 70% (95% CI, 66%-73%) respectively. Rates of ≥very good partial response and complete response were also similar. Any-grade cytokine release syndrome (CRS) was more frequent with GPRC5D BsAbs (57% vs. 74%, p = 0.006), whereas grade ≥3 CRS and other severe toxicities, including neurotoxicity, infections and haematological adverse events (AEs), were broadly comparable. Meta-regression identified prior penta-drug exposure and higher median lines of therapy as negative moderators of response, with prior BCMA-directed therapy further associated with reduced efficacy in BCMA-targeted cohorts. Overall, BCMA- and GPRC5D-targeted BsAbs demonstrated comparable efficacy. Among the commonly reported non-target specific AEs, the safety profile was broadly comparable. The response appeared to be influenced primarily by treatment history.