Background

Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging.

Methods

A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup.

Results

We identified 27 patients who developed nirAEs (20 males, median age 69 years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5 days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5 days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%).

Conclusions

Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.

中文翻译：

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免疫检查点抑制剂治疗期间神经系统不良事件的表征和管理：意大利的多中心经验

背景

神经免疫相关不良事件 (nirAE) 是免疫检查点抑制剂 (ICI) 的罕见毒性。随着ICI肿瘤适应症的增多，其发病率也越来越高。尽管如此，他们的认可和管理仍然具有挑战性。

方法

建立了一个基于网络的全国性数据库，以收集接受 ICI 的患者的神经系统症状病例，并且在充分检查后不能归因于其他原因。

结果

我们确定了 27 名发生 nirAE 的患者（20 名男性，中位年龄 69 岁）。患者接受了抗 PD1/PDL1 (78%)、抗 CTLA4 (4%) 或两者 (19%)。最常见的癌症是黑色素瘤（30%）和非小细胞肺癌（26%）。外周神经系统受到的影响最大（78%）。中位发病时间为 43.5 天，外周和中枢神经系统毒性更短（36 天对 144.5 天，p = 0.045）。常见的表现是肌炎 (33%)、炎症性多发性神经根神经病 (33%) 和重症肌无力 (19%)，单独或联合出现，但诊断范围很广。大多数患者接受了一线糖皮质激素 (85%) 或 IVIg (15%)。7 名患者 (26%) 需要二线治疗。最后一次随访时，4 名 (15%) 患者死亡（脑炎，1 名；肌炎/肌无力伴心肌炎，2 名；急性多发性神经根神经病，1 名），7 名（26%）完全缓解，8 名（30%）部分改善，六个（22%）稳定/进展症状。大多数患者（78%）停止了 ICI 治疗。

结论

神经 irAE 很少见，但可能致命。它们主要影响神经肌肉结构，但包括广泛的表现。必须及时识别及时停止免疫治疗和使用糖皮质激素。对于皮质类固醇或严重受影响的患者，IVIg 或血浆置换的二线治疗可能会带来额外的好处。