Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis

// Tengfei Zhang 1,2,* , Ling Cao 1,3,* , Jing Xie 4,* , Ni Shi 5 , Zhen Zhang 1,3 , Zhenzhen Luo 1,3 , Dongli Yue 1,3 , Zimeng Zhang 6 , Liping Wang 3 , Weidong Han 7 , Zhongwei Xu 8 , Hu Chen 9 and Yi Zhang 1,3,10,11 1 Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2 Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States 3 Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 4 Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia 5 Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States 6 Department of Immunology, Harvard Medical School, Boston, Massachusetts United States 7 Molecular & Immunological/Bio-Therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China 8 Department of Gastroenterology, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania, United States 9 Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science, Beijing, China 10 Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China 11 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China * These authors have contributed equally to this work Correspondence to: Yi Zhang, email: // Keywords : CD19, chimeric antigen receptor, B cell malignancies, meta analysis, efficiency Received : July 06, 2015 Accepted : August 20, 2015 Published : September 10, 2015 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.