Liping Zhao ¹, Chuo Li ², Shiyu Zuo ², Yajing Han ², Biping Deng ³, Zhuojun Ling ⁴, Yanlei Zhang ⁵, Shuixiu Peng ⁵, Jinlong Xu ⁴, Jiajia Duan ⁴, Zelin Wang ⁴, Xinjian Yu ⁶, Qinlong Zheng ⁶, Xiuwen Xu ⁶, Ying Yuan ⁷, Zhenglong Tian ⁸, Kaiting Tang ², Yibing Zhang ², Qing Niu ², Jiecheng Zhang ⁹, Alex H Chang ¹⁰, Yuechen Luo ¹¹, Xiaoming Feng ¹², Jing Pan ¹³

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 CR or CRi. 74% underwent transplantation. Twelve-month progression-free survival with and without censoring transplantation was 22% (95%CI 4-100) and 57% (41-81), respectively. These results support that autologous CD7 CAR T-cell therapy without T-cell pre-selection is feasible in patients with r/r T-ALL.

Refer to the original: https://doi.org/10.1016/j.ymthe.2024.09.006