Safety and efficacy of a humanized CD19 chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic leukemia

• Published in: American journal of hematology Vol. 97; no. 6; pp. 711 - 718
• Main Authors: Shi, Ming, Li, Li, Wang, Shiyuan, Cheng, Hai, Chen, Wei, Sang, Wei, Qi, Kunming, Li, Zhenyu, Wang, Gang, Li, Huizhong, Lan, Jianping, Huang, Jinqi, Fei, Xiaoming, Yu, Min, Li, Fei, Qiao, Jianlin, Wu, Qingyun, Zeng, Lingyu, Jing, Guangjun, Zheng, Junnian, Gale, Robert Peter, Xu, Kailin, Cao, Jiang
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2022; Wiley Subscription Services, Inc
• Subjects: Acute lymphoblastic leukemia; Adaptor Proteins, Signal Transducing; Animals; Antigens; Antigens, CD19; CD19 antigen; Cell Count; Chimeric antigen receptors; Copy number; Hematology; Humans; Immunogenicity; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Mice; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Receptors, Chimeric Antigen; Remission; Single-Chain Antibodies - genetics; Single-Chain Antibodies - therapeutic use
• ISSN: 0361-8609; 1096-8652; 1096-8652
• DOI: 10.1002/ajh.26506

CD19‐targeted chimeric antigen receptor T (CAR‐T) cells using murine single‐chain variable fragment (scFv) has shown substantial clinical efficacy in treating relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, potential immunogenicity of the murine scFv domain may limit the persistence of CAR‐T cells. In this study, we treated 52 consecutive subjects with R/R ALL with humanized CD19‐specific CAR‐T cells (hCART19s). Forty‐six subjects achieved complete remission (CR) (N = 43) or CR with incomplete count recovery (CRi) (N = 3) within 1 month post infusion. During the follow‐up with a median time of 20 months, the 1‐year cumulative incidence of relapse was 25% (95% confidence interval [CI] 13–46), and 1‐year event‐free survival was 45% (95% CI 29–60). To the cutoff date, 20 patients presented CD19+ relapse and 2 had CD19− relapse. Among the 22 relapsed patients, 14 had treatment‐mediated and treatment‐boosted antidrug antibodies (ADA) as detected in a sensitive and specific cell‐based assay. ADA positivity was correlated with the disease relapse risk. ADA‐positive patients had a significantly lower CAR copy number than ADA‐negative patients at the time of recurrence (p < .001). In conclusion, hCART19s therapy is safe and highly active in R/R ALL patients, and the hCART19s treatment could induce the emergence of ADA, which is related to the recurrence of the primary disease.