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

• Anti-BCMA bispecifics failed to improve survival in early relapse post-ide-cel, whereas non-BCMA bispecifics may offer greater efficacy.

• Early relapse, extramedullary disease, and >3 prior treatment lines are key adverse prognostic factors.

Abstract Idecabtagene vicleucel (ide-cel), an adoptive chimeric antigen receptor (CAR) 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 [IQR], 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%CI, 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 (ORR) (≥ partial response) was higher in patients treated with BsAbs (36%) than others (13%, p=0.002). Treatment with non-BCMA BsAbs resulted in significantly higher ORR (67% vs. 30%, p=0.018), OS (19.48 vs. 8.41 months, p=0.034) and PFS (9.2 vs. 3.81 months, p=0.035) 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=0.040), as was extramedullary disease (OS: 13.8 vs 6.28 months, p=0.033) 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. ClinicalTrials.gov identifier NCT04328298