Abstract

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*106 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 8.3months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma.

View details for DOI 10.1038/s41591-022-02182-7

View details for PubMedID 36690811