Chimeric antigen receptor T-cell therapy - assessment and management of toxicities.
Chimeric antigen receptor T-cell therapy - assessment and management of toxicities.
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DOI：
10.1038/nrclinonc.2017.148
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Shpall EJ
中科院分区：
文献类型：
--
作者：
Neelapu SS;Tummala S;Kebriaei P;Wierda W;Gutierrez C;Locke FL;Komanduri KV;Lin Y;Jain N;Daver N;Westin J;Gulbis AM;Loghin ME;de Groot JF;Adkins S;Davis SE;Rezvani K;Hwu P;Shpall EJ
利用经基因工程改造以表达嵌合抗原受体（CAR）的T细胞进行的免疫疗法，正迅速成为治疗血液系统和非血液系统恶性肿瘤的一种有前景的新疗法。CAR - T细胞疗法可诱导快速且持久的临床反应，但伴有独特的急性毒性，这些毒性可能很严重，甚至致命。细胞因子释放综合征（CRS）是最常见的毒性反应，其严重程度从轻度的全身症状到与危及生命的多器官功能障碍相关的重度综合征不等；严重的CRS很少会发展为暴发性噬血细胞性淋巴组织细胞增生症（HLH）。神经毒性，称为CAR - T细胞相关脑病综合征（CRES），是第二常见的不良事件，可与CRS同时发生或在CRS之后发生。对毒性进行密切监测和及时处理对于将这种潜在治愈性治疗方法相关的发病率和死亡率降至最低至关重要；然而，目前缺乏对毒性进行准确且一致的分级和处理的方案。为了满足这一未被满足的需求，我们成立了一个CAR - T细胞疗法相关毒性（CARTOX）工作组，其成员包括来自多个机构和医学学科、有治疗使用各种CAR - T细胞疗法产品患者经验的研究人员。在此，我们描述了我们各机构所采用的多学科方法，并就监测、分级和处理CAR - T细胞疗法治疗患者可能出现的急性毒性提供了建议。
Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.
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影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
11.5
作者：
Deisseroth, Albert;Ko, Chia-Wen;Pazdur, Richard
通讯作者：
Pazdur, Richard
影响因子：
45.3
作者：
Ahmed, Nabil;Brawley, Vita S.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen
影响因子：
20.3
作者：
Fraietta, Joseph A.;Beckwith, Kyle A.;Maus, Marcela V.
通讯作者：
Maus, Marcela V.
影响因子：
56.9
作者：
Bargou, Ralf;Leo, Eugen;Kufer, Peter
通讯作者：
Kufer, Peter