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The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review

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Abstract

CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017. The pooled severe CRS proportion was 29.3% (95% confidence interval [CI] 12.3–49.1%) in B-ALL, 38.8% (95%CI 12.9–67.6%) in B-CLL, and 19.8% (95%CI 4.2–40.8%) in B-NHL. In the univariate meta regression analysis, the proliferation of CD19-CAR-T cell in vivo was correlated with the severe CRS. Specifically, total infusion cell dose contributed to the severe CRS occurring in B-ALL patients but not in B-CLL or B-NHL patients. Tumor burden was strongly associated with the severity of CRS in B-ALL. Besides, post-HSCT CD19 CAR-T cell infusion represented lower severe CRS incidence. Further investigations into the risk factors of CRS in B-CLL and B-NHL are needed.

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Funding

This study was supported by National Natural Sciences Foundation of China (81600151) and Shanghai Municipal Bureau of health and Family Planning Commission (Grants 20154Y0168).

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  1. Zhen Jin and Rufang Xiang contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Ruijin Er Road 197, Shanghai, China

    Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao & Junmin Li

  2. Shanghai Institute of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao & Junmin Li

  3. Department of Laboratory Medicine, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Zizhen Xu

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  1. Zhen Jin
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Contributions

Zhen Jin designed the study, collected the data, preformed the statistical analysis, and wrote the manuscripts. Rufang Xiang collected all the data, performed the statistical analysis, and revised the manuscript. Kai Qing, Xiaoyang Li, Yunxiang Zhang, Hongming Zhu, Lining Wang, and Yuanfei Mao revised the paper. Junmin Li and Zizhen Xu designed the study and revised the manuscript.

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Correspondence to Zizhen Xu or Junmin Li.

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Figure S1

Forest plot of severe CRS incidence in post-HSCT CAR-T cell infusion group and non-HSCT patients group based on disease type. (GIF 97 kb)

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Jin, Z., Xiang, R., Qing, K. et al. The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review. Ann Hematol 97, 1327–1335 (2018). https://doi.org/10.1007/s00277-018-3368-8

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