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

FCARH143, an autologous BCMA-targeted CAR-T therapy which incorporates a fully human BCMA-specific scFv and 4-1BB costimulatory domain, was evaluated in a phase 1 trial (NCT03338972) for relapsed/refractory multiple myeloma (RRMM). Patients were stratified by bone marrow (BM) plasma cell involvement (10-30% or >30%) and received lymphodepleting chemotherapy followed by escalating CAR-T cell doses (50×106 to 450×106). The primary endpoint was safety; secondary endpoints were overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Among 28 enrolled patients, all underwent leukapheresis and successful CAR-T manufacturing, though three (11%) did not proceed to infusion. The 25 treated patients (median age 64 years) had a median of eight prior therapies, 80% were triple-class refractory, and 44% had extramedullary disease (EMD). Cytokine release syndrome (CRS) occurred in 84% (8% grade 3-4, no grade 5), and neurotoxicity in 24% (12% grade 3, 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 anti-myeloma activity with a 100% response rate and manageable toxicity, independent of disease burden or cytogenetic risk. Further evaluation in high-risk RRMM is warranted.