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 vitro cytotoxicity 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: Yongxian Hu, Zhao Wu, Yi Luo, Jimin Shi, Jian Yu, Chengfei Pu, Zuyu Liang, Guoqing Wei, Qu Cui, Jie Sun, Jing Jiang, Jue Xie, Yamin Tan, Wanmao Ni, Jifang Tu, Jinping Wang, Aiyun Jin, Hao Zhang, Zhen Cai, Lei Xiao, He Huang
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 13 Pg. 3297-3306 (07 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28039267 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Antigens, CD19
• CD19 molecule, human
• Receptors, Antigen, T-Cell

Topics

• Adult
• Antigens, CD19 (immunology)
• China
• Disease-Free Survival
• Female
• Graft vs Host Disease (drug therapy, immunology)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Male
• Middle Aged
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (immunology, pathology, therapy)
• Receptors, Antigen, T-Cell (administration & dosage, immunology)
• Recurrence
• Remission Induction
• T-Lymphocytes (drug effects, immunology)