| Abstract: |
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 I experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naïve patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). METHODS In the ALPHA2/ALPHA studies, the safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naïve 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/m2 once daily), cyclophosphamide (300 or 500 mg/m2 once daily), and escalating doses of the anti-CD52 monoclonal antibody, ALLO-647. RESULTS As of September 26, 2024, 33 CD19 CAR T-naïve 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. CONCLUSION Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL. © 2025 by American Society of Clinical Oncology. |
| Keywords: |
adult; clinical article; controlled study; treatment response; aged; middle aged; major clinical study; fludarabine; clinical trial; constipation; fatigue; neutropenia; cancer recurrence; diarrhea; side effect; cancer patient; neoplasm recurrence, local; anemia; nausea; thrombocytopenia; cyclophosphamide; pathology; chill; coughing; fever; lymphocytopenia; hypoxia; hypokalemia; hypotension; immunology; multicenter study; tumor recurrence; peripheral edema; chimeric antigen receptor; lymphoma, large b-cell, diffuse; leukocyte count; phase 1 clinical trial; therapy; adoptive immunotherapy; cell expansion; immunotherapy, adoptive; cd19 antigen; antigens, cd19; hypocalcemia; adverse event; phase 2 clinical trial (topic); decreased appetite; phase 1 clinical trial (topic); cytokine release syndrome; multicenter study (topic); procedures; diffuse large b cell lymphoma; infusion related reaction; humans; human; male; female; article; chimeric antigen receptor t-cell immunotherapy; receptors, chimeric antigen; cemacabtagene ansegedleucel
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