BackgroundImmune‐checkpoint inhibitors (ICIs) often cause immune‐related adverse events (irAEs). The spectrum of irAEs and their managements has been partially clarified, however the knowledge on time‐course of irAEs is not well understood.MethodsA retrospective study based on the medical record was performed. The study subjects were consisting of patients with various types of solid tumors for whom ICIs (nivolumab, pembrolizumab, durvalumab, atezolizumab, nivolumab plus ipilimumab) were used between April 2016 and October 2021. We focused on irAEs developed more than 1‐year after commencement ICIs (delayed irAE group) and compared with irAEs developed within 1‐year (non‐delayed irAE group) in terms of types and severity of irAEs.ResultsA total of 336 patients were enrolled in the study. Eighty‐eight patients (26.2%) developed irAEs and 248 did not. Most of the patients developing irAEs were treated using PD‐L1/PD‐1 inhibitors. Eighty‐one patients (24.1%) in non‐delayed irAE group and 7 patients (2.1%) in delayed irAE group developed irAEs. The median onset of irAEs in the delayed irAE group was 18.6 months (range: 13.5–24.3). The types of irAEs observed in delayed irAE group were dermatitis (2 cases), pneumonitis (2 cases), nephritis (1 case), arthritis (1 case), and gastritis (1 case). The severity of irAEs was almost mild (≤G2), but one patient (.3%) developed G3 nephritis.ConclusionPD‐L1/PD‐1 inhibitors frequently caused various irAEs but their severities were mostly tolerable. Few patients developed delayed irAE with mild toxities.

中文翻译：

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免疫治疗长反应者的迟发性免疫相关不良事件：单中心经验

背景免疫检查点抑制剂（ICIs）经常引起免疫相关不良事件（irAE）。 irAE 的谱系及其处理方法已部分明确，但对 irAE 时程的了解尚不清楚。方法根据病历进行回顾性研究。研究受试者由 2016 年 4 月至 2021 年 10 月期间使用 ICI（nivolumab、pembrolizumab、durvalumab、atezolizumab、nivolumab 加 ipilimumab）的各种类型实体瘤患者组成。我们重点关注开始后 1 年多发生的 irAE ICI（延迟性irAE组）与1年内发生的irAE（非延迟性irAE组）在irAE的类型和严重程度方面进行比较。 结果 共有336名患者纳入研究。 88 名患者 (26.2%) 出现了 irAE，248 名患者没有出现。大多数出现 irAE 的患者都使用 PD-L1/PD-1 抑制剂进行治疗。非迟发性 irAE 组中的 81 名患者（24.1%）和迟发性 irAE 组中的 7 名患者（2.1%）出现了 irAE。延迟性 irAE 组中 irAE 的中位发病时间为 18.6 个月（范围：13.5-24.3）。延迟irAE组中观察到的irAE类型为皮炎（2例）、肺炎（2例）、肾炎（1例）、关节炎（1例）和胃炎（1例）。 irAE 的严重程度几乎为轻度（≤G2），但 1 例患者（0.3%）发展为 G3 肾炎。结论 PD-L1/PD-1 抑制剂经常引起各种 irAE，但其严重程度大多是可以忍受的。很少有患者出现迟发性 irAE 并伴有轻度毒性。