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.

使用经过基因工程改造以表达嵌合抗原受体 (CAR) 的 T 细胞的免疫疗法正迅速成为血液学和非血液学恶性肿瘤的一种有前途的新疗法。CAR-T 细胞疗法可以诱导快速和持久的临床反应，但与独特的急性毒性有关，这种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，其严重程度从低度全身症状到与危及生命的多器官功能障碍相关的高级综合征不等；极少数情况下，严重的 CRS 会演变成暴发性噬血细胞性淋巴组织细胞增多症 (HLH)。神经毒性，称为 CAR-T 细胞相关性脑病综合征 (CRES)，是第二常见的不良事件，可与 CRS 同时或在 CRS 之后发生。密切监测和及时处理毒性对于最大限度地减少与这种潜在治愈性治疗方法相关的发病率和死亡率至关重要；然而，缺乏准确和一致的毒性分级和管理算法。为了解决这一未满足的需求，我们成立了一个 CAR-T 细胞疗法相关毒性 (CARTOX) 工作组，由来自多个机构和医学学科的研究人员组成，他们具有使用各种 CAR-T 细胞疗法产品治疗患者的经验。在此，我们描述了我们机构采用的多学科方法，并提供了监测、分级和管理接受 CAR-T 细胞治疗的患者可能发生的急性毒性的建议。