Anti-GPRC5D CAR-T Cells(Institute of Hematology & Blood Diseases Hospital)

Although chimeric antigen receptor (CAR)‐T cells targeting B‐cell maturation antigen (BCMA) have significantly advanced multiple myeloma (MM) therapy, many patients eventually progress, prompting the search for the most effective salvage regimens. To address this demand, we performed a random‐effects meta‐analysis evaluating response rates to salvage treatments after anti‐BCMA CAR‐T failure. We identified 36 eligible studies comprising 476 patients and seven distinct interventions through systematic database screening. Among them, bispecific antibodies (bsAbs) were the most common choice, followed by anti‐BCMA CAR‐T cells. We separately assessed response rates to both first‐ and any subsequent (combined)‐line salvage interventions. In the first‐line setting, selinexor‐based regimens yielded the highest overall response rates (ORR) of 67% (95% CI: 38%–91%), followed by bsAbs (60%; 95% CI: 43%–76%). In the combined setting, anti‐GPRC5D CAR‐T cells achieved the highest ORR (88%; 95% CI: 65%–100%), followed by anti‐BCMA CAR‐T cells (75%; 95% CI: 42%–98%). Belantamab mafodotin demonstrated the lowest efficacy (0%; 95% CI: 0%–17%). Complete response rates remained low across all interventions (range: 0%–40%). Heterogeneity investigations revealed superior responses with human/humanized anti‐BCMA CAR‐T constructs compared with the animal‐based receptors. In summary, our meta‐analysis suggested that CAR‐T cells and bsAbs are suitable for salvage use after anti‐BCMA CAR‐T failure in MM.Trial Registration: PROSPERO number: CRD42024621077