Iwamoto Yuichiro, Kimura Tomohiko, Dan Kazunori, Iwamoto Hideyuki, Sanada Junpei, Fushimi Yoshiro, Katakura Yukino, Shimoda Masashi, Nakanishi Shuhei, Mune Tomoatsu, Kaku Kohei, Kaneto Hideaki
Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.
Sci Rep. 2025 Jan 2;15(1):390. doi: 10.1038/s41598-024-84488-9.
The purpose of this study was to analyze the efficacy of treatment and survival after administration of immune checkpoint inhibitor (ICI) in Japanese patients and had endocrine-related and/or other immune-related adverse events (irAEs), as well as irAEs in multiple organs. This is a single-center, retrospective, observational study of 571 Japanese patients treated with ICI at our hospital. We evaluated the occurrence of Grade 3 or higher irAEs and the life expectancy and treatment efficacy after ICI administration. Endocrine-related irAE (E-irAE), other irAE (O-irAE), endocrine-related and other irAE (EO-irAE), and multiple endocrine-related irAE (ME-irAE) were evaluated in groups. 80.8% of patients had an irAE, with the highest incidence of irAE with ipilimumab plus PD-1 inhibitor, followed by atezolizumab 59.0%, pembrolizumab 53.7%, avelumab 50.0%, and nivolumab 47.3%, Durvamumab 26.7% followed; Kaplan-Meier survival curves showed higher survival rates in patients with irAE compared to non-irAE, and higher survival rates in EO-irAE and ME-irAE compared to E-irAE and O-irAE (p < 0.001). The COX proportional hazard ratios for overall survival were E-irAE 0.611 (0.480-0.772), O-irAE 0.758 (0.597-0.957), EO-irAE 0.622 (0.466-0.819) and ME-irAE 0.463 when non-irAE was set at 1.000 (0.257-0.775). When grade 3 or higher irAEs appeared, regardless of their type, there was a trend toward higher survival and post-treatment remission rates after ICI administration. In addition to this, patients with irAEs in multiple endocrine tissues and patients with irAEs in both endocrine and other organs had a better response to treatment after ICI administration.
本研究旨在分析免疫检查点抑制剂（ICI）给药后，日本内分泌相关和/或其他免疫相关不良事件（irAE）以及多器官irAE患者的治疗效果和生存率。这是一项针对我院571例接受ICI治疗的日本患者的单中心回顾性观察研究。我们评估了3级或更高级别irAE的发生情况以及ICI给药后的预期寿命和治疗效果。对内分泌相关irAE（E-irAE）、其他irAE（O-irAE）、内分泌相关和其他irAE（EO-irAE）以及多内分泌相关irAE（ME-irAE）进行分组评估。80.8%的患者出现irAE，伊匹木单抗联合PD-1抑制剂的irAE发生率最高，其次是阿特珠单抗59.0%、帕博利珠单抗53.7%、阿维鲁单抗50.0%、纳武利尤单抗47.3%、度伐利尤单抗26.7%；Kaplan-Meier生存曲线显示，与无irAE的患者相比，有irAE的患者生存率更高，与E-irAE和O-irAE相比，EO-irAE和ME-irAE的生存率更高（p＜0.001）。以无irAE为1.000时，总生存的COX比例风险比分别为：E-irAE 0.611（0.480 - 0.772）、O-irAE 0.758（0.597 - 0.957）、EO-irAE 0.622（0.466 - 0.819）和ME-irAE 0.463（0.257 - 0.775）。当出现3级或更高级别irAE时，无论其类型如何，ICI给药后的生存率和治疗后缓解率都有升高的趋势。除此之外，多内分泌组织出现irAE的患者以及内分泌和其他器官均出现irAE的患者在ICI给药后对治疗的反应更好。
