Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia
Purpose: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor-modified T cells against CD19 (CART19) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. Experimental Design: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine-and cyclophosphamide-based lymphodepletion. The postinfusion responses, toxicities, expansion, and persistence of CART19s in enrolled patients were observed and monitored. Results: We enrolled 15 patients with R/R ALL. The median transduction efficiency of CART19s was 33%. In vitro cytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 x 10(6)/kg to 9.8 x 10(6)/kg. Twelve patients achieved complete remission 1 month after CART19s infusion. CART19s expanded and persisted in peripheral blood and bone marrow. At 150 days, the overall survival rate and leukemia-free survival rate were 65.5% and 37.8%, respectively. The cumulative incidence of relapse and the nonrelapse mortality rate were 54.5% and 7.7%, respectively. Four patients underwent subsequent haploidentical hematopoietic stem cell transplantation. In this trial, 10 patients experienced cytokine release syndrome (CRS). Grade 3 CRS developed in 40% of patients and was associated with a higher disease burden on day -1 and a higher number of previous relapses. Conclusions: This trial demonstrated potent antileukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation. (C) 2016 AACR.
基金:
973 ProgramNational Basic Research Program of China; Innovative Cellular Therapeutics Co., Ltd.; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province; Natural Science Foundation of ChinaNational Natural Science Foundation of China; Zhejiang Medical Technology Education; Science and Technology Department of Zhejiang Province
第一作者机构:[1]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China;
通讯作者:
通讯机构:[1]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China;[2]Innovat Cellular Therapeut Co Ltd, SiDanSai Biotechnol Co Ltd, Shanghai, Peoples R China;[7]Innovat Cellular Therapeut Co Ltd, Room 201,Bldg 4,998 Halei Rd, Shanghai 201203, Peoples R China
推荐引用方式(GB/T 7714):
Hu Yongxian,Wu Zhao,Luo Yi,et al.Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia[J].CLINICAL CANCER RESEARCH.2017,23(13):3297-3306.doi:10.1158/1078-0432.CCR-16-1799.
APA:
Hu, Yongxian,Wu, Zhao,Luo, Yi,Shi, Jimin,Yu, Jian...&Huang, He.(2017).Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia.CLINICAL CANCER RESEARCH,23,(13)
MLA:
Hu, Yongxian,et al."Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia".CLINICAL CANCER RESEARCH 23..13(2017):3297-3306