School of Medicine, Cardiff University, Cardiff, UK.
Department of Neurology, Cardiff and Vale University Health Board, Cardiff, UK.
J Neurol. 2021 Apr;268(4):1544-1554. doi: 10.1007/s00415-020-10237-3. Epub 2020 Nov 2.
Chimeric antigen receptor (CAR)-expressing T cells now offer an effective treatment option for people with previously refractory B cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR-T cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR-T cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate admission to the intensive care unit and is rarely fatal. As CAR-T therapies enter routine clinical practice, it is important for neurologists to be aware of the nature of neurological complications. Here, we summarise the clinical manifestations, mechanisms, investigations and recommended treatment of CAR-T-related neurotoxicity, focusing on the licensed CD19 products.
嵌合抗原受体 (CAR)-表达 T 细胞现在为以前难治性 B 细胞恶性肿瘤患者提供了一种有效的治疗选择,并且正在广泛开发用于治疗多种其他肿瘤。然而,神经毒性是 CAR-T 细胞治疗的常见并发症,在一些队列中超过 50%的接受者中可见。自 2018 年以来,术语“免疫效应细胞相关神经毒性综合征 (ICANS)”已被用于描述和分级 CAR-T 细胞和其他类似疗法后出现的神经毒性。CAR-T 治疗后的 ICANS 通常是自限性的,但可能需要入住重症监护病房,并且很少致命。随着 CAR-T 疗法进入常规临床实践,神经科医生了解神经并发症的性质非常重要。在这里,我们总结了 CAR-T 相关神经毒性的临床表现、机制、检查和推荐治疗方法,重点介绍了已批准的 CD19 产品。