Phase 1 trial of anti-BCMA CAR T-cell therapy for relapsed or refractory AL amyloidosis

The use of anti-BCMA CAR T-cell therapy (CART) for AL amyloidosis (AL) is limited owing to patient frailty. A phase 1 study at the Hebrew University of Jerusalem (Israel) evaluated HBI0101 anti-BCMA CART for AI. The study included 16 patients, most of whom received 800 x 10⁶ CARTs. Patients had received a median four previous lines of therapy (range 3-10). Fourteen of 16 patients were triple class refractory, and 6 were refractory to belantamab. Thirteen of 16 patients had cardiac involvement, including five with MAYO stage IIIa/IIIb at study entry. Cytokine release syndrome was frequent (14/16) but mostly low grade (grade 3: 3/16; no grade 4 or 5). No neurologic toxicity or treatment-related deaths were observed. The overall hematologic response rate was 94% and complete response rate was 75%. Minimal residual disease negativity was achieved in 9 of 14 evaluable patients. Eight of 13 evaluable patients achieved an objective organ response. Seven patients died during long-term follow-up; three while in complete or very good partial response. The median overall survival was 10.1 months (95% CI 5.8-NR). The authors conclude that HBI0101 had acceptable and manageable toxicity with remarkable efficacy among patients with relapsed or refractory AL amyloidosis.