Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, Pa.
Division of Cellular Therapy and Stem Cell Transplant, Hospital of the University of Pennsylvania, Philadelphia, Pa; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa.
J Allergy Clin Immunol. 2020 Nov;146(5):940-948. doi: 10.1016/j.jaci.2020.07.025. Epub 2020 Aug 6.
Chimeric antigen receptor T cells are a new and exciting immunotherapeutic approach to managing cancer, with impressive efficacy but potentially life-threatening inflammatory toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with severe CRS may develop capillary leak syndrome and disseminated intravascular coagulation, with a cytokine signature similar to that of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Moderate-to-severe CRS is managed with the IL-6 receptor antagonist tocilizumab with or without corticosteroids, with questions remaining regarding the optimal management of nonresponders. ICANS is an inflammatory neurotoxicity typically occurring after CRS and characterized by impaired blood-brain barrier integrity. Symptoms of encephalopathy range from mild confusion and aphasia to somnolence, obtundation, and in some cases seizures and cerebral edema. ICANS is currently managed with corticosteroids; however, the optimal dose and duration remain to be determined. Little information is available to guide the management of patients with steroid-refractory ICANS. Numerous cytokine-targeted therapies have been proposed to manage these inflammatory toxicities, but few clinical data are available. Management of inflammatory toxicities of chimeric antigen receptor T cells often requires multidisciplinary management and intensive care, during which allergists and immunologists may encounter patients with these unique toxicities.
嵌合抗原受体 T 细胞是一种用于癌症治疗的新型免疫疗法,具有显著疗效,但也可能导致危及生命的炎症毒性,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)。严重 CRS 患者可能会发生毛细血管渗漏综合征和弥散性血管内凝血,细胞因子特征与巨噬细胞活化综合征/噬血细胞性淋巴组织细胞增多症相似。中重度 CRS 采用白细胞介素-6 受体拮抗剂托珠单抗联合或不联合皮质类固醇治疗,对于无应答者的最佳治疗方法仍存在疑问。ICANS 是一种炎症性神经毒性,通常在 CRS 之后发生,其特征是血脑屏障完整性受损。脑病症状从轻度意识模糊和失语到嗜睡、昏迷,在某些情况下还会出现癫痫发作和脑水肿。ICANS 目前采用皮质类固醇治疗;然而,最佳剂量和持续时间仍有待确定。对于类固醇难治性 ICANS 患者,几乎没有信息可用于指导其管理。已经提出了许多细胞因子靶向疗法来治疗这些炎症毒性,但很少有临床数据。嵌合抗原受体 T 细胞的炎症毒性的管理通常需要多学科管理和重症监护,在此期间,过敏症专家和免疫学家可能会遇到这些具有独特毒性的患者。
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