Phase I trial validating a simplified autologous CD7 CAR-T manufacturing process without T-cell pre-selection, expanding accessibility for pediatric r/r T-ALL patients

Publication Brief

Phase I trial validating a simplified autologous CD7 CAR-T manufacturing process without T-cell pre-selection, expanding accessibility for pediatric r/r T-ALL patients.

Abstract

 Chimeric antigen receptor (CAR)-T cell therapy showed preliminary activity in  patients with refractory or relapsed T cell acute lymphoblastic leukemia (r/r  T-ALL). However, many obstacles remain, including manufacturing difficulties and  risk of infections. This phase I study (NCT04840875) evaluated autologous CD7  CAR-T cells manufactured without pre-selection of healthy T cells in r/r T-ALL.  Thirty patients (29 children and one adult) with a median of two lines of prior  therapy but without detectable peripheral leukemia were enrolled. Excluding  three cases of manufacturing failures, a total of 27 (90%) patients received  infusions after products were confirmed free of leukemia contamination,  including 16 (59%) meeting planned target doses. Common adverse events within 30  days included grade 3-4 cytopenias (100%), grade 1-2 (70%) and 3-4 (7%,  including one dose-limiting toxicity) cytokine release syndrome, grade 1  neurotoxicity (7%), grade 2 infection (4%), and grade 2 graft-versus-host  disease (4%). Two patients developed grade 2 infections after day 30. At day 30,  96% responded and 85% achieved complete remission (CR) or CR with incomplete  hematologic recovery (CRi). Seventy-four percent underwent transplantation.  Twelve-month progression-free survival with and without censoring  transplantation was 22% (95% confidence interval 4%-100%) and 57% (41%-81%),  respectively. These results support that autologous CD7 CAR-T therapy without T  cell pre-selection is feasible in patients with r/r T-ALL. 

Journal: Mol Ther. 2024 Sep 7.

Volume / Pages: S1525-0016(24)00594-X

DOI: 10.1016/j.ymthe.2024.09.006

PubMed: PubMed: 39244642