Increased risk of Lambert-Eaton myasthenic syndrome (LEMS) in small-cell lung cancer patients treated with immune checkpoint inhibitor
Increased risk of Lambert-Eaton myasthenic syndrome (LEMS) in small-cell lung cancer patients treated with immune checkpoint inhibitor
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使用免疫检查点抑制剂治疗的小细胞肺癌患者患兰伯特-伊顿肌无力综合征 (LEMS) 的风险增加
DOI：
10.1016/j.ejca.2022.11.023
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发表时间：
2023
影响因子：
8.4
通讯作者：
Suzuki Shigeaki
中科院分区：
文献类型：
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作者：
Imai Shungo;Mitsuboshi Satoru;Hori Satoko;Suzuki Shigeaki
最近，几种免疫检查点抑制剂（ICIs）的给药适应症扩大到包括小细胞肺癌（SCLC）。然而，ICIs 有一个主要缺点，即通过阻断免疫检查点分子而诱发免疫相关不良事件 (irAE)。兰伯特-伊顿肌无力综合征 (LEMS) 是一种众所周知的副肿瘤性神经综合征 (PNS)，尤其与 SCLC 相关[1]。日本于 2017 年进行的一项 LEMS 全国调查发现了 348 名患者，日本 LEMS 患病率估计为 100 万分之 2.7，与其他国家相似[2]。 LEMS 是由针对突触前神经末梢电压门控钙通道的致病性自身抗体引起的，并导致以近端肌肉无力、反射消失和自主神经功能障碍为特征的神经肌肉接头疾病[3]。考虑到这些，对 SCLC 患者施用 ICI 可能会增加 LEMS 的风险。在这里，为了检验这一假设，我们使用日本药物不良事件报告（JADER）数据库进行了一项回顾性观察研究，因为它对于评估罕见不良事件的风险很有用。JADER数据库是日本药物相关不良事件的自发报告系统，由日本药品和医疗器械机构管理。 JADER 由匿名患者数据组成，因此不需要机构审查委员会的批准。 2004年4月至2022年6月的数据于2022年7月3日从PMDA网站（http://www.pmda.go.jp/）下载。JADER中的不良事件根据监管活动医学词典（MedDRA）进行定义，MedDRA控制词汇中LEMS的“首选术语（PT）”是肌无力综合征（JADER仅提供PT）。
Recently, the indication for administration of several immune checkpoint inhibitors (ICIs) was expanded to include small-cell lung cancer (SCLC). However, ICIs have major downside, that is, immune-related adverse events (irAEs) induced by blocking immune checkpoint molecules. Lambert-Eaton myasthenic syndrome (LEMS) is one of well-known paraneoplastic neurological syndrome (PNS) especially associated with SCLC [1]. A national survey of LEMS in Japan conducted in 2017 identified 348 patients, and the prevalence of LEMS in Japan was estimated at 2.7 in 1,000,000, which is similar to those in other countries [2]. LEMS is caused by pathogenic autoantibodies targeting voltage-gated calcium channels in pre-synaptic nerve terminals and leads to neuromuscular junction disorder characterized by proximal muscle weakness, areflexia, and autonomic dysfunction [3]. Considering these, administration of ICIs to SCLC patients may increase the risk of LEMS. Here, to test this hypothesis, we performed a retrospective observational study using the Japanese Adverse Drug Event Report (JADER) database because it is useful for assessing the risk of rare adverse events.The JADER database is a spontaneous reporting system for drug-related adverse events in Japan and is managed by the Japanese Pharmaceuticals and Medical Devices Agency. JADER is comprised by anonymized patient data and thus approval by institutional review board is not required. Data from April 2004 to June 2022 were downloaded from the PMDA website (http://www. pmda. go. jp/) on July 3, 2022. Adverse events in JADER are defined according to Medical Dictionary for Regulatory Activities (MedDRA), and the “preferred term (PT)” for LEMS in MedDRA's controlled vocabulary is myasthenic syndrome (JADER provides only PTs).