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Clin Cancer Res. 2017 Jul 1;23(13):3297-3306. doi: 10.1158/1078-0432.CCR-16-1799. Epub 2016 Dec 30.

Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia.

Author information

1
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
2
Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China.
3
Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
4
Department of Blood Transfusion, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
5
Clinical Research Center, Zhejiang Provincial People's Hospital, Hangzhou, China.
6
Institute of Hematology, School of Medicine, Zhejiang University, Hangzhou, China.
7
Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China. huanghe@zju.edu.cn Xiaolei@sidansai.com.
8
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. huanghe@zju.edu.cn Xiaolei@sidansai.com.

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.

PMID:
28039267
DOI:
10.1158/1078-0432.CCR-16-1799
[Indexed for MEDLINE]
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