title: Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis.
abstract: Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed (p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cao
authors.affiliation: Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Ni
authors.initials: N
authors.lastname: Shi
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Yue
authors.affiliation: Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Zimeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Molecular & Immunological/Bio-Therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science, Beijing, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China.|School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D018941:Antigens, CD19 / Q000737:chemistry*; D017321:Clinical Trials, Phase I as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000737:chemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012044:Regression Analysis; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D018941:Antigens, CD19; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell
keywords: B cell malignancies; CD19; chimeric antigen receptor; efficiency; meta analysis