各种类型癌症日本患者内分泌相关免疫相关不良事件的发生率。

Incidence of endocrine-related immune-related adverse events in Japanese subjects with various types of cancer.

机构信息

Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.

出版信息

Front Endocrinol (Lausanne). 2023 Jan 23;14:1079074. doi: 10.3389/fendo.2023.1079074. eCollection 2023.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs), such as cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein 1 (PD-1) inhibitors, and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors, are often used to treat a variety of malignancies. ICIs are known to cause endocrine-related immune-related adverse events (irAEs), but the incidence varies among reports and/or agents. This study evaluated the incidence of endocrine-related irAEs in patients who were treated with ICIs in Japan.

METHOD

This single-center, retrospective, observational study examined the incidence and clinical characteristics of endocrine-related irAEs in 466 participants who were treated with ICIs at Kawasaki Medical School Hospital.

RESULT

The mean age of participants with and without endocrine-related irAEs was 69.1 ± 1.8 years and 68.1 ± 1.1 years, respectively, with no difference between them. The overall incidence of any endocrine-related irAEs among the participants was 25.5%. Hypothyroidism was prevalent in 24.3%, hypoadrenocorticism in 3.2%, hypopituitarism in 0.9%, and insulin-dependent diabetes mellitus in 1.1%. Participants receiving combination therapy with CTLA-4 and PD-1 inhibitors had a significantly higher incidence of endocrine-related irAEs than those receiving monotherapy.

CONCLUSION

Endocrine-related irAEs correlated significantly with survival and mean observation period. There was substantial difference in the incidence of endocrine-related irAEs among various types of ICIs and types of cancer. We should bear in mind that endocrine testing is necessary during the treatment with ICIs.

摘要

背景

免疫检查点抑制剂(ICIs),如细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)抑制剂、程序性细胞死亡蛋白 1(PD-1)抑制剂和程序性细胞死亡蛋白 1 配体 1(PD-L1)抑制剂,常用于治疗多种恶性肿瘤。已知 ICI 会引起内分泌相关免疫相关不良事件(irAEs),但不同报告和/或药物的发生率不同。本研究评估了在日本接受 ICI 治疗的患者中发生内分泌相关 irAEs 的发生率。

方法

这是一项单中心、回顾性、观察性研究,研究了在川崎医科大学医院接受 ICI 治疗的 466 名参与者中内分泌相关 irAEs 的发生率和临床特征。

结果

有和无内分泌相关 irAEs 的参与者的平均年龄分别为 69.1±1.8 岁和 68.1±1.1 岁,无差异。参与者中任何内分泌相关 irAEs 的总发生率为 25.5%。甲状腺功能减退症的发生率为 24.3%,肾上腺皮质功能减退症为 3.2%,垂体功能减退症为 0.9%,胰岛素依赖型糖尿病为 1.1%。接受 CTLA-4 和 PD-1 抑制剂联合治疗的参与者内分泌相关 irAEs 的发生率明显高于接受单药治疗的参与者。

结论

内分泌相关 irAEs 与生存和平均观察期显著相关。不同类型的 ICI 和癌症类型的内分泌相关 irAEs 的发生率存在显著差异。我们应该记住,在接受 ICI 治疗期间需要进行内分泌检查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead3/9899881/ef4f880ba183/fendo-14-1079074-g001.jpg

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