Department of Neurology, Research Institute and Hospital of National Cancer Center, 323 Ilsan-Ro, Ilsandong-gu, Goyang, Korea.
J Cancer Res Clin Oncol. 2023 Aug;149(9):5583-5589. doi: 10.1007/s00432-022-04516-x. Epub 2022 Dec 10.
Neuromuscular immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) have been increasingly recognized as a consequence of expanding use of ICIs in advanced cancers. We aimed to evaluate the frequency, phenotypes, rescue treatment, and clinical outcomes of severe neuromuscular irAEs of ICIs at National Cancer Center (NCC), Korea.
Consecutive patients with newly developed severe neuromuscular irAEs (common terminology criteria for adverse events grade 3 or greater) after ICI treatment at NCC in Korea between December 2018 and April 2022 were included by searching neuromuscular diagnostic codes in electronic medical records and/or reviewing neurological consultation documentations.
Of the 1,503 ICI-treated patients, nine (0.6%) experienced severe neuromuscular irAEs; five with pembrolizumab and four with atezolizumab. The patients included five women and four men; their median age at onset was 59 years. The irAEs included Guillain-Barre syndrome (n = 5) and myasthenia gravis (MG) crisis with myositis (n = 4), and developed after a median of one (range 1-5) ICI cycle. The median modified Rankin score (mRS) was 4 (range 3-5) at the nadir. ICIs were discontinued in all patients, and rescue immunotherapy included corticosteroids (n = 9), intravenous immunoglobulin (n = 7), and plasmapheresis (n = 2). Eight patients showed improvements, with a median mRS of 3 (range 1-4); however, one patient (who had MG crisis with myocarditis) died.
In this real-world monocentric study, ICI-induced neuromuscular irAEs were rare but potentially devastating; thus, physicians should remain vigilant to enable prompt recognition and management of irAEs.
随着免疫检查点抑制剂(ICI)在晚期癌症中的广泛应用,越来越多的人认识到与免疫相关的不良事件(irAE)会导致神经肌肉不良事件。本研究旨在评估韩国国家癌症中心(NCC)ICI 治疗后严重神经肌肉 irAE 的发生频率、表型、抢救治疗和临床结局。
通过在电子病历中搜索神经肌肉诊断代码和/或回顾神经科会诊记录,纳入 2018 年 12 月至 2022 年 4 月期间在韩国 NCC 新诊断出严重神经肌肉 irAE(不良事件通用术语标准 3 级或更高)的连续 ICI 治疗患者。
在 1503 例接受 ICI 治疗的患者中,有 9 例(0.6%)发生严重神经肌肉 irAE;5 例接受 pembrolizumab 治疗,4 例接受 atezolizumab 治疗。患者包括 5 名女性和 4 名男性;发病中位年龄为 59 岁。irAE 包括格林-巴利综合征(n=5)和重症肌无力(MG)危象伴肌炎(n=4),发病中位时间为 1 个 ICI 周期(范围 1-5 个)。最低 mRS 中位数为 4(范围 3-5)。所有患者均停用 ICI,抢救免疫治疗包括皮质类固醇(n=9)、静脉注射免疫球蛋白(n=7)和血浆置换(n=2)。8 例患者病情改善,mRS 中位数为 3(范围 1-4);然而,1 例(MG 危象伴心肌炎)患者死亡。
在这项真实世界的单中心研究中,ICI 诱导的神经肌肉 irAE 罕见但可能具有破坏性;因此,医生应保持警惕,以便及时识别和处理 irAE。