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帕博利珠单抗诱导的自身免疫性脑炎的临床特征、诊断及治疗

Clinical features, diagnosis, and treatment of pembrolizumab induced autoimmune encephalitis.

作者信息

Zou Li, Rao Xianlin, Zhao Xiyue

机构信息

Department of Pharmacy, Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, Xihu District, Hangzhou, Zhejiang, 310012, China.

Department of Infectious Disease, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China.

出版信息

Invest New Drugs. 2025 Apr;43(2):191-198. doi: 10.1007/s10637-025-01511-0. Epub 2025 Feb 5.

Abstract

Pembrolizumab has shown links to autoimmune encephalitis (AE), yet the exact clinical characteristics remain unclear. This study examines the clinical features of pembrolizumab-induced AE to enhance diagnostic accuracy and therapeutic strategies. Reports on pembrolizumab-induced AE were gathered via a searchable database, culminating on November 30, 2024. The median age at onset among the 34 patients was 68 years (range 47-82), with males constituting 67.6%. The average onset period for AE was 6 months (range 0.3-25) after the initial dose, with an average of 6 cycles (range 1-17). Commonly reported symptoms included confusion (38.2%), fever (35.3%), and decreased consciousness (32.4%). Cerebrospinal fluid analysis revealed elevated protein (55.9%), leukocytosis (70.6%), and normal blood glucose levels (38.2%). Antineuronal antibodies were found to be negative in 41.2% of cases and positive in 35.3%. Magnetic resonance imaging indicated T2/FLAIR hypersignal in 32.4% of cases, while the electroencephalogram revealed slow waves (11.8%) and diffuse slowing (11.8%). Following treatment with steroids, intravenous immunoglobulin, and plasmapheresis, 82.4% of patients experienced symptom improvement or recovery, though 5.9% succumbed to AE. Oncologists must consider the risk of AE when prescribing pembrolizumab. Early diagnosis and intervention for AE are crucial. Further research is needed to define the optimal treatment approach.

摘要

帕博利珠单抗已显示出与自身免疫性脑炎(AE)有关联,但其确切的临床特征仍不清楚。本研究旨在探讨帕博利珠单抗诱导的AE的临床特征,以提高诊断准确性和治疗策略。通过一个可搜索的数据库收集了关于帕博利珠单抗诱导的AE的报告,截止日期为2024年11月30日。34例患者的中位发病年龄为68岁(范围47 - 82岁),男性占67.6%。AE的平均发病时间为初始剂量后的6个月(范围0.3 - 25个月),平均为6个周期(范围1 - 17个周期)。常见报告症状包括意识模糊(38.2%)、发热(35.3%)和意识减退(32.4%)。脑脊液分析显示蛋白升高(55.9%)、白细胞增多(70.6%),血糖水平正常(38.2%)。41.2%的病例抗神经元抗体为阴性,35.3%为阳性。磁共振成像显示32.4%的病例有T2/FLAIR高信号,而脑电图显示慢波(11.8%)和弥漫性减慢(11.8%)。在接受类固醇、静脉注射免疫球蛋白和血浆置换治疗后,82.4%的患者症状改善或恢复,尽管有5.9%的患者死于AE。肿瘤学家在开具帕博利珠单抗处方时必须考虑AE的风险。对AE进行早期诊断和干预至关重要。需要进一步研究来确定最佳治疗方法。

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