Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Clin Oncol. 2024 Jul;21(7):501-521. doi: 10.1038/s41571-024-00903-0. Epub 2024 May 20.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of several haematological malignancies and is being investigated in patients with various solid tumours. Characteristic CAR T cell-associated toxicities such as cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are now well-recognized, and improved supportive care and management with immunosuppressive agents has made CAR T cell therapy safer and more feasible than it was when the first regulatory approvals of such treatments were granted in 2017. The increasing clinical experience with these therapies has also improved recognition of previously less well-defined toxicities, including movement disorders, immune effector cell-associated haematotoxicity (ICAHT) and immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), as well as the substantial risk of infection in patients with persistent CAR T cell-induced B cell aplasia and hypogammaglobulinaemia. A more diverse selection of immunosuppressive and supportive-care pharmacotherapies is now being utilized for toxicity management, yet no universal algorithm for their application exists. As CAR T cell products targeting new antigens are developed, additional toxicities involving damage to non-malignant tissues expressing the target antigen are a potential hurdle. Continued prospective evaluation of toxicity management strategies and the design of less-toxic CAR T cell products are both crucial for ongoing success in this field. In this Review, we discuss the evolving understanding and clinical management of CAR T cell-associated toxicities.
嵌合抗原受体 (CAR) T 细胞疗法已经彻底改变了几种血液恶性肿瘤的治疗方法，并且正在各种实体瘤患者中进行研究。现在已经很好地认识到了特征性的 CAR T 细胞相关毒性，如细胞因子释放综合征 (CRS) 和免疫效应细胞相关神经毒性综合征 (ICANS)，并且通过免疫抑制药物进行了改进的支持性护理和管理，使得 CAR T 细胞疗法比 2017 年首次获得此类治疗的监管批准时更安全、更可行。随着这些疗法的临床经验不断增加，人们对以前定义不太明确的毒性也有了更好的认识，包括运动障碍、免疫效应细胞相关血液毒性 (ICAHT) 和免疫效应细胞相关噬血细胞性淋巴组织细胞增生综合征 (IEC-HS)，以及在持续性 CAR T 细胞诱导的 B 细胞无功能和低丙种球蛋白血症患者中存在严重感染风险。现在，为了毒性管理，更多种类的免疫抑制和支持性护理药物治疗正在被应用，但还没有普遍适用于这些药物的应用算法。随着针对新抗原的 CAR T 细胞产品的开发，涉及表达靶抗原的非恶性组织损伤的额外毒性是一个潜在的障碍。持续前瞻性评估毒性管理策略和设计毒性较小的 CAR T 细胞产品对于该领域的持续成功都是至关重要的。在这篇综述中，我们讨论了对 CAR T 细胞相关毒性的不断发展的认识和临床管理。
