Salvage Therapies After Anti-BCMA CAR-T Failure in Patients With Multiple Myeloma: A Meta-Analysis of Response Rates

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.