title: Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia.
abstract: 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 vitrocytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 × 106/kg to 9.8 × 106/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.Clin Cancer Res; 23(13); 3297-306. ©2016 AACR.
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Pu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zuyu
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Blood Transfusion, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Xie
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yamin
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Clinical Research Center, Zhejiang Provincial People's Hospital, Hangzhou, China.
authors.forename: Wanmao
authors.initials: W
authors.lastname: Ni
authors.affiliation: Institute of Hematology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Tu
authors.affiliation: Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Aiyun
authors.initials: A
authors.lastname: Jin
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China. huanghe@zju.edu.cn Xiaolei@sidansai.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. huanghe@zju.edu.cn Xiaolei@sidansai.com.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology*; D002681:China; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage / Q000276:immunology*; D012008:Recurrence; D012074:Remission Induction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; D011948:Receptors, Antigen, T-Cell