Kimura Sakiko, Katsuya Hiroo, Nakashima Chiho, Sueoka-Aragane Naoko, Hayashida Koji, Sasaki Kazumi, Sogawa Rintaro, Furuno Tatsuya, Yamauchi Moriyasu, Sugiyama Yoichiro, Noshiro Hirokazu, Esaki Motohiro, Noguchi Mitsuru, Takahashi Hirokazu, Anzai Keizo, Yokoyama Masatoshi, Sugita Kazunari, Yamashita Yoshio, Kawaguchi Atsushi, Kimura Shinya, Shimanoe Chisato
Department of Pharmacy, Saga University Hospital, 5-1-1 Nabeshima, Saga City, Saga, 849-8501, Japan.
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga City, Saga, Japan.
BMC Immunol. 2025 Apr 16;26(1):33. doi: 10.1186/s12865-025-00711-w.
Immune-checkpoint inhibitors (ICIs) can cause inflammation and immune-related adverse events (irAEs). Although irAEs may be caused by dysregulation of cytokines, the impact of various COVID- 19-related factors on expression of ICI-related AEs remains unclear. Assessment of AEs following ICI administration during the COVID- 19 pandemic may provide valuable insights that enable optimization of patient selection, thereby maximizing the benefits of ICI therapy. The aim of this study was to investigate the actual occurrence of severe AEs after ICI administration during the COVID- 19 pandemic. The medical records of patients who received ICI at Saga University Hospital were examined retrospectively. The primary endpoint was the incidence of all AEs ≥ Grade 3 that occurred after ICI administration. The survey period, from Jan 2020 to Dec 2022, was divided into an earlier (Jan 2020-March 2021) and a later (April 2021-Dec 2022) period. AEs with a clear cause other than ICI were excluded from the analysis. A total of 527 patients were included in the analysis, with a median follow-up of 422 days. During the COVID- 19 pandemic, the incidence of AEs ≥ Grade 3 after ICI administration was 52.8%. The incidence of AEs ≥ Grade 3 AEs after ICI administration was significantly higher during the later period [23.4% (57/244) in the earlier period and 49.8% (236/474) in the later period; mixed effect model p < 0.0001, odds ratio, 3.37 (95% CI: 2.32-4.89)]. Overall survival was significantly worse in the group with AEs ≥ Grade 3 than in the group without AEs ≥ Grade 3 [HR (95% CI) = 0.48 (0.36-0.65), p = 0.0001]. During the COVID- 19 pandemic, it became clear that the incidence of severe AEs (including irAEs) increased after ICI administration, particularly during the later period of the disease. Various factors may be associated with occurrence of severe AEs after ICI administration, and long-term careful observation and prospective multicenter clinical studies are required.
免疫检查点抑制剂（ICIs）可引发炎症和免疫相关不良事件（irAEs）。尽管irAEs可能由细胞因子失调引起，但各种与新冠病毒病（COVID-19）相关的因素对ICI相关不良事件表达的影响仍不明确。在COVID-19大流行期间评估ICI给药后的不良事件，可能会提供有价值的见解，有助于优化患者选择，从而使ICI治疗的益处最大化。本研究的目的是调查在COVID-19大流行期间ICI给药后严重不良事件的实际发生情况。对在佐贺大学医院接受ICI治疗的患者的病历进行了回顾性检查。主要终点是ICI给药后发生的所有≥3级不良事件的发生率。调查期从2020年1月至2022年12月分为早期（2020年1月至2021年3月）和后期（2021年4月至2022年12月）。分析中排除了由ICI以外明确原因引起的不良事件。共有527例患者纳入分析，中位随访时间为422天。在COVID-19大流行期间，ICI给药后≥3级不良事件的发生率为52.8%。ICI给药后≥3级不良事件的发生率在后期显著更高[早期为23.4%（57/244），后期为49.8%（236/474）；混合效应模型p<0.0001，比值比为3.37（95%CI：2.32-4.89）]。≥3级不良事件组的总生存期显著低于无≥3级不良事件组[HR（95%CI）=0.48（0.36-0.65），p=0.0001]。在COVID-19大流行期间，很明显ICI给药后严重不良事件（包括irAEs）的发生率增加，尤其是在疾病后期。各种因素可能与ICI给药后严重不良事件的发生有关，则需要进行长期仔细观察和前瞻性多中心临床研究。
