Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results

In an interim phase 1 trial analysis, escalating doses of off-the-shelf allogeneic anti-BCMA CAR T cells, in combination with an anti-CD52 antibody-containing lymphodepletion regimen, were feasible to administer and exhibited an encouraging safety profile in patients with relapsed or refractory multiple myeloma ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen. Key secondary endpoints were response rate and duration of response. Grade >= 3 adverse events were reported in 38 (88.0%) of patients. Cytokine release syndrome was observed in 24 patients (55.8%), with 1 grade >= 3 event (2.3%) and neurotoxicity in 6 patients (14%), with no grade >= 3 events. Infections occurred in 23 patients (53.5%), with 10 (23.3%) of grade >= 3. Overall, 24 patients (55.8%) had a response. Among patients treated with 320 x 10(6) CAR(+) T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n = 24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma.