Department of Hepatology and Gastroenterology.
Department of Diagnostic and Interventional Radiology, Charité University Medicine Berlin.
Medicine (Baltimore). 2021 Jun 18;100(24):e26377. doi: 10.1097/MD.0000000000026377.
On the basis of the results of the IMBRAVE-150 trial, the combination of atezolizumab, a programmed cell death ligand 1 (PD-L1) antibody, as well as bevacizumab, a vascular endothelial growth factor (VEGF) antibody, represents a promising novel first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Despite favorable safety data, serious adverse events have been described. However, central nervous system complications such as encephalitis have rarely been reported. We present the case of a 70-year-old woman with hepatitis C virus (HCV)-related liver cirrhosis and advanced HCC who developed severe encephalitis after only one cycle of atezolizumab/bevacizumab.
Ten days after administration, the patient presented with confusion, somnolence, and emesis. Within a few days, the patient's condition deteriorated, and mechanical ventilation became necessary.
Cerebrospinal fluid (CSF) analysis showed increased cell count and elevated protein values. Further work-up revealed no signs of an infectious, paraneoplastic, or other autoimmune cause.
Suspecting an atezolizumab/bevacizumab-related encephalitis, we initiated a high-dose steroid pulse therapy as well as repeated plasmapheresis, which resulted in clinical improvement and remission of CSF abnormalities.
Despite successful weaning and transfer to a rehabilitation ward, the patient died of progressive liver cancer 76 days after initial treatment with atezolizumab/bevacizumab, showing no response.
This case illustrates that rapid immunosuppressive treatment with prednisolone can result in remission even of severe encephalitis. We discuss this case in the context of available literature and previously reported cases of atezolizumab-induced encephalitis in different tumor entities, highlighting the diagnostic challenges in oncologic patients treated with immune checkpoint-inhibitors.
基于 IMBRAVE-150 试验的结果,阿替利珠单抗(一种程序性死亡配体 1 [PD-L1] 抗体)与贝伐珠单抗(一种血管内皮生长因子 [VEGF] 抗体)的联合治疗代表了晚期肝细胞癌(HCC)患者有前途的新型一线治疗选择。尽管安全性数据良好,但已描述了严重的不良事件。然而,中枢神经系统并发症,如脑炎,很少有报道。我们报告了一例 70 岁女性病例,患有丙型肝炎病毒(HCV)相关肝硬化和晚期 HCC,在接受阿替利珠单抗/贝伐珠单抗治疗仅一个周期后就发生了严重脑炎。
给药后 10 天,患者出现意识模糊、嗜睡和呕吐。几天后,患者病情恶化,需要进行机械通气。
脑脊液(CSF)分析显示细胞计数增加和蛋白值升高。进一步检查未发现感染、副肿瘤或其他自身免疫原因的迹象。
怀疑与阿替利珠单抗/贝伐珠单抗相关的脑炎,我们开始进行大剂量类固醇脉冲治疗和重复血浆置换,这导致临床改善和 CSF 异常的缓解。
尽管成功脱机并转至康复病房,但患者在接受阿替利珠单抗/贝伐珠单抗初始治疗后 76 天死于进展性肝癌,无反应。
本例表明,用泼尼松龙进行快速免疫抑制治疗甚至可以缓解严重脑炎。我们在可用文献和以前报道的不同肿瘤实体中阿替利珠单抗诱导的脑炎病例的背景下讨论了这个病例,强调了在接受免疫检查点抑制剂治疗的肿瘤患者中诊断的挑战。