Allogeneic CAR T Cell Products Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Experience From the ALPHA2/ALPHA Clinical Studies

Purpose Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T cell products may improve access to treatment versus autologous ones. We report the phase 1 experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naive patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Patients and Methods In the ALPHA2/ALPHA studies, safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naive patients with R/R LBCL. Patients received healthy donor-derived, human leukocyte antigen–unmatched cema-cel/ALLO-501 following a 3-day lymphodepletion regimen of fludarabine (30 mg/m 2 /day), cyclophosphamide (300 or 500 mg/m 2 /day), and escalating doses of the anti-CD52 monoclonal antibody, ALLO-647. Results As of September 26, 2024, 33 CD19 CAR T-naive patients with LBCL (median age, 66 years; median number of prior therapies, 3) received allogeneic CAR T cells. CAR T cell expansion was observed following infusion, with persistence observed up to 4 months. Overall and complete response rates were 58% and 42%, respectively; median duration of response in patients with a complete response was 23.1 months. The most common treatment-emergent adverse events were hematologic toxicities. No cases of graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome, or grade ≥3 cytokine release syndrome were reported. Conclusion Allogeneic CD19 CAR T cells demonstrated promising overall and durable complete response rates with a manageable safety profile in CD19 CAR T-naive patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL.