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

Annals of Hematology
Zhen JinJunmin Li

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...Continue Reading

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Citations

Jun 13, 2019·Hematological Oncology·David Sermer, Renier Brentjens
Oct 24, 2019·Recent Patents on Anti-cancer Drug Discovery·Romeo G Mihăilă
Jul 25, 2020·Intensive Care Medicine·Elie AzoulaySandrine Valade
Jan 24, 2021·Journal of Biomedical Science·Tomasz Klaus, Sameer Deshmukh
Dec 29, 2020·Journal for Immunotherapy of Cancer·Sattva S NeelapuMichael R Bishop
Nov 21, 2020·International Journal of Molecular Sciences·Wen-Ying LinYi-Yen Lee
Apr 16, 2020·Acta Biomaterialia·Waqas NawazZhiwei Wu
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Apr 29, 2021·Drug and Therapeutics Bulletin·Kayleigh Kew
Sep 14, 2021·The Cochrane Database of Systematic Reviews·Moritz ErnstMarius Goldkuhle
Oct 7, 2021·Scientific Reports·Ditte E JæhgerThomas L Andresen

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