{"title":"在复发/难治性 T-ALL 儿科患者中未进行 T 细胞预选而生成的自体 CD7 CAR T 细胞:I 期试验。","authors":"Liping Zhao, Chuo Li, Shiyu Zuo, Yajing Han, Biping Deng, Zhuojun Ling, Yanlei Zhang, Shuixiu Peng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Ying Yuan, Zhenglong Tian, Kaiting Tang, Yibing Zhang, Qing Niu, Jiecheng Zhang, Alex H Chang, Yuechen Luo, Xiaoming Feng, Jing Pan","doi":"10.1016/j.ymthe.2024.09.006","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":null,"pages":null},"PeriodicalIF":12.1000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Autologous CD7 CAR T cells generated without T-cell pre-selection in pediatric patients with relapsed/refractory T-ALL: a phase I trial.\",\"authors\":\"Liping Zhao, Chuo Li, Shiyu Zuo, Yajing Han, Biping Deng, Zhuojun Ling, Yanlei Zhang, Shuixiu Peng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Ying Yuan, Zhenglong Tian, Kaiting Tang, Yibing Zhang, Qing Niu, Jiecheng Zhang, Alex H Chang, Yuechen Luo, Xiaoming Feng, Jing Pan\",\"doi\":\"10.1016/j.ymthe.2024.09.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":19020,\"journal\":{\"name\":\"Molecular Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.1000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ymthe.2024.09.006\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2024.09.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Autologous CD7 CAR T cells generated without T-cell pre-selection in pediatric patients with relapsed/refractory T-ALL: a phase I trial.
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.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.