A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up.

abstractFCARH143, an autologous B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, which incorporates a fully human BCMA-specific single chain variable fragment and 4-1BB costimulatory domain, was evaluated in a phase 1 trial for relapsed/refractory multiple myeloma (RRMM). Patients were stratified by bone marrow plasma cell involvement (10%-30% or >30%) and received lymphodepleting chemotherapy followed by escalating CAR-T doses (50 × 106 to 450 × 106). The primary end point was safety; secondary end points were overall response rate (ORR), duration of response, and progression-free survival (PFS). Among 28 enrolled patients, all underwent leukapheresis and successful CAR-T manufacturing, although 3 (11%) did not proceed to infusion. The 25 treated patients (median age, 64 years) had a median of 8 prior therapies, 80% were triple-class refractory, and 44% had extramedullary disease. Cytokine release syndrome occurred in 84% (8% grade 3-4 and no grade 5), and neurotoxicity in 24% (12% grade 3 and no grade 4-5). No treatment-related deaths occurred. At a median follow-up of 67.3 months, treated patients had an ORR of 100%, including a stringent complete response in 64%. Median PFS and overall survival (OS) were 15.5 and 32.1 months, respectively. In an intention-to-treat analysis (median follow-up, 69.6 months), the ORR was 89.3%, and OS was 30.2 months. FCARH143 demonstrated potent antimyeloma activity, with a 100% response rate and manageable toxicity, independent of disease burden or cytogenetic risk. Further evaluation in high-risk RRMM is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03338972.