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

Vollständiger Abstract

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Summary 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.