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Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies

Authors :
Chunrui Li
Xuelian Hu
Qiuxiang Wang
Lijun Jiang
Yicheng Zhang
Xiaoxi Zhou
Wenyue Cao
Haodong Cai
Yang Cao
Miao Zheng
Yaoyao Lou
Tongcun Zhang
Liang Huang
Xia Mao
Jiali Cheng
Di Wang
Jianfeng Zhou
Dandan Yan
Liting Chen
Na Wang
Gaoxiang Wang
Yi Xiao
Shangkun Zhang
Chaojiang Gu
Source :
Blood. 135(1)
Publication Year :
2019

Abstract

Antigen-escape relapse has emerged as a major challenge for long-term disease control after CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. From March 2016 through January 2018, we conducted a pilot study in 89 patients who had refractory/relapsed B-cell malignancies, to evaluate the efficacy and safety of sequential infusion of anti-CD19 and anti-CD22, a cocktail of 2 single-specific, third-generation chimeric antigen receptor-engineered (CAR19/22) T cells. Among the 51 patients with acute lymphoblastic leukemia, the minimal residual disease-negative response rate was 96.0% (95% confidence interval [CI], 86.3-99.5). With a median follow-up of 16.7 months (range, 1.3-33.3), the median progression-free survival (PFS) was 13.6 months (95% CI, 6.5 to not reached [NR]), and the median overall survival (OS) was 31.0 months (95% CI, 10.6-NR). Among the 38 patients with non-Hodgkin lymphoma, the overall response rate was 72.2% (95% CI, 54.8-85.8), with a complete response rate of 50.0% (95% CI, 32.9-67.1). With a median follow-up of 14.4 months (range, 0.4-27.4), the median PFS was 9.9 months (95% CI, 3.3-NR), and the median OS was 18.0 months (95% CI, 6.1-NR). Antigen-loss relapse occurred in 1 patient during follow-up. High-grade cytokine release syndrome and neurotoxicity occurred in 22.4% and 1.12% patients, respectively. In all except 1, these effects were reversible. Our results indicated that sequential infusion of CAR19/22 T cell was safe and efficacious and may have reduced the rate of antigen-escape relapse in B-cell malignancies. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526.

Details

ISSN :
15280020
Volume :
135
Issue :
1
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....8c0a06a59a12ffc443d518bd3c43cc11