Spotlight on Tocilizumab in the Treatment of CAR-T-Cell-Induced Cytokine Release Syndrome: Clinical Evidence to Date

被引:77
作者
Si, Stephanie [1 ,2 ]
Teachey, David T. [1 ,2 ]
机构
[1] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
chimeric antigen receptor-T-cell therapy; cytokine release syndrome; tocilizumab; pediatric; ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY; ACUTE LYMPHOBLASTIC-LEUKEMIA; RHEUMATOID-ARTHRITIS; B-CELL; MACROPHAGE ACTIVATION; SOLUBLE IL-6; FOLLOW-UP; THERAPY; BLINATUMOMAB; PHARMACOKINETICS;
D O I
10.2147/TCRM.S223468
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
Immune-based therapies such as chimeric antigen receptor (CAR)-T-cell therapy have revolutionized the landscape of cancer treatment in recent years. Although this class of therapy has demonstrated impressive clinical efficacy against cancers that were once thought to be incurable, its success is in part limited by unique toxicities which can be severe or even fatal. Cytokine release syndrome (CRS) is the most commonly observed toxicity and occurs as a result of non-antigen specific immune activation. Similar to macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH), CRS is associated with elevated levels of several cytokines including interleukin-6 (IL-6) that serve as a driver for host immune dysregulation. As a direct anti-cytokine drug, tocilizumab has been a cornerstone in the treatment of CAR-T-associated CRS through its ability to dampen CRS without compromising CAR-T-cell function. However, optimal timing of administration is yet unknown. Here, we review the use of tocilizumab in the management of CAR-T-associated CRS, emphasizing on the clinical efficacy across various CAR constructs and its role in current CRS management algorithms. We also discuss alternative therapies that may be considered for refractory CRS therapy and the use of tocilizumab in the current COVID-19 global pandemic.
引用
收藏
页码:705 / 714
页数:10
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