Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study

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Abstract
Idecabtagene vicleucel (ide-cel), an adoptive chimeric antigen receptor T-cell therapy directed against B-cell maturation antigen (BCMA), has demonstrated high response rates and improved survival in patients with relapsed/refractory multiple myeloma. However, all patients eventually relapse, and data on salvage therapy outcomes remain limited. We conducted a national, real-world study of 154 patients relapsing after ide-cel, with a median time to progression of 6.0 months (interquartile range, 3.0-9.9). Salvage therapies included anti-BCMA bispecific antibodies (BsAbs) (n = 79), non-BCMA BsAbs targeting GPRC5D or FcRH5 (n = 12), combinations of immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody (n = 40), and others (n = 23). Median overall survival (OS) was 12.12 months (95% confidence interval, 6.6 to not reached), and median progression-free survival (PFS) was 3.48 months (95% CI, 2.6-6.37). The overall response rate (≥ partial response) was higher in patients treated with BsAbs (36%) than others (13%, P = .002). Treatment with non-BCMA BsAbs resulted in significantly higher ORR (67% vs 30%, P = .018), OS (19.48 vs 8.41 months, P = .034) and PFS (9.2 vs 3.81 months, P = .035) compared to anti-BCMA BsAbs. Early relapse after ide-cel (≤6 months) was associated with worse outcomes (OS: 5.95 vs 12.58 months, P = .040), as was extramedullary disease (OS: 13.8 vs 6.28 months, P = .033) and exposure to >3 prior lines of therapy. In summary, anti-BCMA BsAbs offered limited efficacy whereas non-BCMA BsAbs may offer a promising therapeutic approach following ide-cel early relapse. These results underscore the potential benefits of diversifying targets in relapse post-ide-cel treatment strategies. This trial was registered at www.clinicaltrials.gov as #NCT04328298.

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