MM-530 Interventions and Outcomes of Multiple Myeloma Patients Progressing after BCMA-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy

BCMA-targeted treatments, including CAR-T therapy and bispecific antibodies (Abs), have established remarkable efficacy for relapsed/refractory multiple myeloma (RRMM). With approval of ide-cel and cilta-cel, CAR-T is quickly becoming more widely used. However, prognosis, clinical outcomes, and treatment approaches of patients with MM with relapse after BCMA CAR-T therapy have not been described comprehensively. We collected disease characteristics and post-study outcomes of MM patients with progression of disease after treatment with BCMA CAR-T at 2 academic centers. We identified 140 patients treated with BCMA CAR-T, of which 79 had relapsed disease with ≥1 salvage therapy and were included in this analysis. Median time between MM diagnosis and relapse after BCMA CAR-T (T0) was 74 months. Patients were highly pretreated with median of 5 prior lines (range 1-18) and 64 patients (81.0%) had high-risk characteristics by FISH. Of the 79 patients, 66 (83.5%) were triple-class refractory and 30 patients (38.0%) were penta-drug refractory. Five patients (6.3%) had received prior treatment with (non-BCMA) bispecific Ab. Patients received a median of 2 (range 1-10) salvage treatments. The objective response rate to the first regimen after T0 was 43.8% with a median progression-free survival (PFS1) of 3.5 months. The most common initial salvage treatments were triplets including approved agents (n=33, 41.8%), combination chemotherapy (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide (VD-PACE) or bortezomib, dexamethasone, cyclophosphamide, etoposide, cisplatin ((V)DCEP)) (n=13, 16.5%), or a bispecific Ab trial (n=11, 13.9%). Median overall survival (OS) from T0 for the cohort was 17.9 months (14.0-NE months). In total, 35 patients received T cell-redirecting therapy (CAR-T or bispecific Ab) at any point after CAR-T relapse, including second/subsequent salvage regimens. Of note, OS was significantly longer (median not reached, p<0.001) in the 35 patients that received another T cell-redirecting therapy at any point after BCMA CAR-T relapse. In summary, MM patients with relapse after BCMA CAR-T can be salvaged. The choice for specific salvage therapies should be guided by patient characteristics. Development of novel therapies, including immune-mediated treatments, offers potential for multiple lines of salvage therapy contributing to the observed OS, which compares favorably to previous reports of triple-class refractory MM patients.