免疫检查点抑制剂相关胃肠道免疫相关不良事件的临床特征及其与生存的关系。

Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival.

机构信息

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya City 4668560, Aichi, Japan.

Department of Endoscopy, Nagoya University Hospital, Nagoya City 4668560, Aichi, Japan.

出版信息

World J Gastroenterol. 2021 Nov 7;27(41):7190-7206. doi: 10.3748/wjg.v27.i41.7190.

DOI:10.3748/wjg.v27.i41.7190

PMID:34887637

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8613649/

Abstract

BACKGROUND

Despite the popularity of immune checkpoint inhibitors (ICIs) in the treatment of advanced cancer, patients often develop gastrointestinal (GI) and non-GI immune-related adverse events (irAEs). The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports. This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment.

AIM

To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs.

METHODS

In this single-center, retrospective, observational study, we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020. We analyzed the clinical characteristics of patients who received ICI treatment. We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer (LC) and malignant melanoma (MM). Kaplan-Meier analysis was used to compare the median overall survival (OS). Multivariate Cox proportional hazards models were used to identify prognostic factors. A value < 0.05 was considered statistically significant.

RESULTS

GI-irAEs occurred in 34 of 605 patients (5.6%) treated with an anti-programmed cell death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibody alone and in nine of 56 patients (16.1%) treated with an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies. The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies ( < 0.05). In 130 patients with MM, OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs ( = 0.035). In contrast, in 209 patients with non-small cell LC, there was no significant difference in OS between the groups. The multivariate analyses showed that a performance status of 2-3 (hazard ratio: 2.406; 95% confidence interval: 1.125-5.147; = 0.024) was an independent predictive factor for OS in patients with MM.

CONCLUSION

Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies. Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

摘要

背景

尽管免疫检查点抑制剂 (ICIs) 在治疗晚期癌症方面广受欢迎，但患者经常会出现胃肠道 (GI) 和非 GI 免疫相关不良事件 (irAEs)。以前的报告并未充分阐明 GI-irAEs 的临床特征和生存结局。因此，需要评估 GI-irAEs 对接受 ICI 治疗的患者的影响。

目的

评估 GI-irAEs 的临床特征及其对接受 ICI 治疗的患者生存的影响。

方法

在这项单中心、回顾性、观察性研究中，我们回顾了 2014 年 9 月至 2020 年 8 月期间在名古屋大学医院接受 ICI 治疗的 661 例各种癌症患者的记录。我们分析了接受 ICI 治疗的患者的临床特征。我们还评估了 GI-irAE 发展与非小细胞肺癌 (LC) 和恶性黑色素瘤 (MM) 患者预后之间的相关性。使用 Kaplan-Meier 分析比较中位总生存期 (OS)。使用多变量 Cox 比例风险模型确定预后因素。 < 0.05 被认为具有统计学意义。

结果

单独使用抗程序性细胞死亡蛋白-1/程序性死亡配体 1 (抗 PD-1/PD-L1) 抗体治疗的 605 例患者中有 34 例 (5.6%) 和单独使用抗细胞毒性 T 淋巴细胞抗原 4 (抗 CTLA-4) 抗体治疗的 56 例患者中有 9 例 (16.1%) 发生了 GI-irAEs。单独使用抗 CTLA-4 抗体或联合使用抗 PD-1 和抗 CTLA-4 抗体的患者，累积发病率和中位每日腹泻频率明显更高 ( < 0.05)。在 130 例 MM 患者中，与未发生 GI-irAEs 的患者相比，尽管发生了 GI-irAEs，但继续接受 ICI 治疗的患者的 OS 明显延长 ( = 0.035)。相比之下，在 209 例非小细胞 LC 患者中，两组间 OS 无显著差异。多变量分析显示，2-3 级表现状态 (风险比：2.406；95%置信区间：1.125-5.147； = 0.024) 是 MM 患者 OS 的独立预测因素。