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

被引:37
|
作者
Jin, Zhen [1 ,2 ]
Xiang, Rufang [1 ,2 ]
Qing, Kai [1 ,2 ]
Li, Xiaoyang [1 ,2 ]
Zhang, Yunxiang [1 ,2 ]
Wang, Lining [1 ,2 ]
Zhu, Hongming [1 ,2 ]
Mao, Yuanfei [1 ,2 ]
Xu, Zizhen [3 ]
Li, Junmin [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Hematol, Sch Med, Ruijin Er Rd 197, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Ruijin Hosp, Sch Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Lab Med, Sch Med, Shanghai, Peoples R China
关键词
CD19 chimeric antigen receptor T cell; Cytokine release syndrome; Acute lymphoblastic leukemia; Chronic lymphoblastic leukemia; B-cell non-Hodgkin lymphoma; CHIMERIC-ANTIGEN-RECEPTOR; CAR-T-CELLS; B-CELL; REMISSIONS; LYMPHOMA; MALIGNANCIES; TRANSPLANTATION; PERSISTENCE; BIOMARKERS; LEUKEMIA;
D O I
10.1007/s00277-018-3368-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1327 / 1335
页数:9
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