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

Authors

Frederick L Locke
Javier L Munoz
Michael T Tees
Lazaros J Lekakis
Sven de Vos
Rajneesh Nath
Don A Stevens
Shahbaz A Malik
Geoffrey P Shouse
Mehdi Hamadani
Olalekan O Oluwole
Miguel-Angel Perales
David B Miklos
Paul W Fisher
Amy Feng
Lynn Navale
John B Le Gall
Sattva S Neelapu

Publication Date

5-10-2025

Journal

Journal of Clinical Oncology

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.

Trial registration: ClinicalTrials.gov NCT04416984 NCT03939026.

Keywords

Adult, Aged, Female, Humans, Male, Middle Aged, Antigens, CD19, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Neoplasm Recurrence, Local, Receptors, Chimeric Antigen

DOI

10.1200/JCO-24-01933

PMID

39946666

PMCID

PMC12058369

PubMedCentral® Posted Date

2-13-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes