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新型癌症免疫疗法所致中枢神经系统损伤。

Central nervous system injury from novel cancer immunotherapies.

机构信息

MGH Cancer Center.

Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Curr Opin Neurol. 2020 Dec;33(6):723-735. doi: 10.1097/WCO.0000000000000867.

Abstract

PURPOSE OF REVIEW

Neurotoxicity from antineoplastic treatment remains a challenge in oncology. Cancer treatment-induced central nervous system (CNS) injury can be therapy-limiting, severely disabling, and even fatal. While emerging cancer immunotherapies have revolutionized oncology during the past decade, their immunomodulatory properties can cause immune-related adverse effects (IRAE) across organ systems, including the nervous system. Central neurologic IRAEs from chimeric antigen receptor T cells (CAR-T) and immune checkpoint inhibitors (ICPI) are challenging complications of such therapies.We aim to provide clinicians with a comprehensive review of the relevant forms of CAR-T and ICPI-associated CNS toxicity, focusing on clinical features of such complications, diagnostic workup, predictive biomarkers, and management considerations in affected patients.

RECENT FINDINGS

Unique forms of CAR-T and ICPI-related CNS toxicity have been characterized in the recent literature. CAR-T-related neurotoxicity is common and clinically well delineated. ICPI-related CNS toxicity is relatively rare but includes a heterogenous spectrum of severe and diagnostically challenging conditions. While putative risk factors, neurotoxicity biomarkers, imaging correlates and treatment strategies have been put forward, development of tailored diagnostic and management consensus guidelines awaits further clinical investigation.

SUMMARY

As CAR-T and ICPI become more widely adopted, early recognition, documentation, and management of immunotherapy-related CNS toxicity are of paramount importance in the clinical setting.

摘要

目的综述

抗肿瘤治疗引起的神经毒性仍然是肿瘤学领域的一个挑战。癌症治疗引起的中枢神经系统(CNS)损伤可能会限制治疗,严重致残,甚至致命。虽然新兴的癌症免疫疗法在过去十年中彻底改变了肿瘤学,但它们的免疫调节特性会导致免疫相关的不良反应(irAE)发生在包括神经系统在内的各个器官系统中。嵌合抗原受体 T 细胞(CAR-T)和免疫检查点抑制剂(ICPI)引起的中枢神经系统 irAE 是这些治疗方法的严重并发症。我们旨在为临床医生提供有关 CAR-T 和 ICPI 相关 CNS 毒性的综合综述,重点介绍这些并发症的临床特征、诊断评估、预测生物标志物以及受影响患者的管理注意事项。

最新发现

最近的文献中已经描述了独特形式的 CAR-T 和 ICPI 相关 CNS 毒性。CAR-T 相关神经毒性很常见,临床表现明确。ICPI 相关的 CNS 毒性相对较少,但包括一系列严重且具有挑战性的诊断条件。虽然已经提出了推测的危险因素、神经毒性生物标志物、影像学相关性和治疗策略,但需要进一步的临床研究来制定针对这些毒性的定制诊断和管理共识指南。

总结

随着 CAR-T 和 ICPI 的广泛应用,在临床环境中,早期识别、记录和管理免疫治疗相关的 CNS 毒性至关重要。

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