• Na Wang, Xuelian Hu, Wenyue Cao, Chunrui Li, Yi Xiao, Yang Cao, Chaojiang Gu, Shangkun Zhang, Liting Chen, Jiali Cheng, Gaoxiang Wang, Xiaoxi Zhou, Miao Zheng, Xia Mao, Lijun Jiang, Di Wang, Qiuxiang Wang, Yaoyao Lou, Haodong Cai, Dandan Yan, Yicheng Zhang, Tongcun Zhang, Jianfeng Zhou, and Liang Huang.
• Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
• Blood. 2020 Jan 2; 135 (1): 17-27.

AbstractAntigen-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.© 2020 by The American Society of Hematology.

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