异基因 CAR-T 细胞产品 Cemacabtagene Ansegedleucel/ALLO-501 治疗复发/难治性大 B 细胞淋巴瘤：ALPHA2/ALPHA 临床研究的 I 期经验

Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T-cell products may improve access to treatment versus autologous ones. We report the phase I experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-na ve patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).

In the ALPHA2/ALPHA studies, the safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-na ve 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 once daily), cyclophosphamide (300 or 500 mg/m 2 once daily), and escalating doses of the anti-CD52 monoclonal antibody, ALLO-647.

As of September 26, 2024, 33 CD19 CAR T-na ve patients with LBCL (median age, 66 years; median number of previous therapies, 3) received allogeneic CAR T cells. CAR T-cell expansion was observed following infusion, with persistence observed up to 4 months. The overall and complete response (CR) rates were 58% and 42%, respectively; the median duration of response in patients with a CR 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.

Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-na ve patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL.