Palazzo Leonardo, Pieri Valentina, Berzero Giulia, Filippi Massimo
Neurology Unit, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
Faculty of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy.
Brain Sci. 2024 Nov 30;14(12):1220. doi: 10.3390/brainsci14121220.
The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood-brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR-T cells observed in systemic B-cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers. Early studies conducted in adult and paediatric patients with solid CNS tumours reported a distinct profile of neurotoxicity referred to as Tumour inflammation-associated neurotoxicity (TIAN), corresponding to local inflammation at the tumour site manifesting with focal neurological deficits or mechanical complications (e.g., obstructive hydrocephalus). The present review summarises available data on the efficacy and safety of CAR-T cells for solid and haematological CNS malignancies, emphasising known and emerging phenotypes, ongoing challenges, and future perspectives.
嵌合抗原受体（CAR）-T细胞的出现最近改变了复发/难治性弥漫性大B细胞淋巴瘤的预后，缓解率高达60%至80%。关键临床试验中报告的常见毒性包括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），这是一种与髓样细胞激活和血脑屏障功能障碍相关的刻板脑病，表现为一系列独特的书写障碍、失语、定向障碍、注意力缺陷、警觉性受损、运动症状、癫痫发作和弥漫性脑水肿。在系统性B细胞恶性肿瘤中观察到的CAR-T细胞巨大的肿瘤学疗效，导致其在原发性或继发性中枢神经系统（CNS）淋巴瘤患者以及实体瘤患者（包括几种CNS癌症）中的使用越来越多。在成年和儿科实体CNS肿瘤患者中进行的早期研究报告了一种称为肿瘤炎症相关神经毒性（TIAN）的独特神经毒性特征，对应于肿瘤部位的局部炎症，表现为局灶性神经功能缺损或机械性并发症（如梗阻性脑积水）。本综述总结了关于CAR-T细胞治疗实体和血液系统CNS恶性肿瘤的疗效和安全性的现有数据，强调了已知和新出现的表型、持续存在的挑战以及未来展望。
