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预测肺癌老年患者免疫检查点抑制剂相关不良反应的因素:一项前瞻性真实世界分析。

Predictors of immune checkpoint inhibitor-related adverse events in older patients with lung cancer: a prospective real-world analysis.

机构信息

Department of Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Graduate School Peking Union Medical College, Beijing, 100730, China.

出版信息

J Cancer Res Clin Oncol. 2023 Sep;149(11):8993-9006. doi: 10.1007/s00432-023-04792-1. Epub 2023 May 10.

Abstract

PURPOSE

Older patients with cancer are underrepresented in pivotal trials of immune checkpoint inhibitors (ICIs). This study aimed to investigate immune-related adverse events (irAEs) that occur in older patients with lung cancer treated with ICIs, and explore predictors of the occurrence of irAEs.

METHODS

A prospective analysis was performed on older patients with lung cancer aged ≥ 65 years who were treated with anti-programmed cell death-1/-ligand 1 (PD-1/PD-L1) inhibitors in Beijing Hospital from January 2018 to December 2022. The incidence and risk factors of irAEs were estimated by the Chi-square test or Wilcoxon rank-sum tests. The predictive power of Geriatric-8 (G-8) for irAEs was tested by receiver operating characteristic (ROC) curve analysis. Lymphocyte counts were measured by flow cytometry. Cytokine levels were tested by Enzyme-linked immunosorbent assay, respectively. Kaplan-Meier method was used to calculated progression-free survival (PFS) curves, and the log-rank test was used to evaluate differences.

RESULTS

A total of 201 older patients aged ≥ 65 years with lung cancer were enrolled in this study. The most common irAEs were interstitial pneumonia, dermatological toxicity and hypothyroidism, with rates of 17.2%, 16.1% and 5.6%, respectively. ROC showed that G-8 could predict the occurrence of irAEs in patients aged 65-71 years (≥ G2 irAEs: AUC = 0.757, p < 0.001; ≥ G3 irAEs: AUC = 0.862, p < 0.001), but not for patients aged ≥ 71 years. NLR, LMR, PNI, hypertension and diabetes were associated with irAEs. Lower CD4 + T cells and B cells, and lower levels of IL-10 were associated with the development of irAEs.

CONCLUSION

Our study confirmed the accuracy of G-8 for predicting irAEs in older patients. We also identified several predictors of irAEs in older patients with lung cancer.

摘要

目的

在免疫检查点抑制剂(ICI)的关键试验中,癌症老年患者代表性不足。本研究旨在调查接受 ICI 治疗的老年肺癌患者发生的免疫相关不良事件(irAE),并探讨 irAE 发生的预测因素。

方法

对 2018 年 1 月至 2022 年 12 月在北京医院接受抗程序性细胞死亡蛋白-1/配体 1(PD-1/PD-L1)抑制剂治疗的年龄≥65 岁的老年肺癌患者进行前瞻性分析。采用卡方检验或 Wilcoxon 秩和检验估计 irAE 的发生率和危险因素。通过受试者工作特征(ROC)曲线分析评估老年 8 项(G-8)预测 irAE 的能力。通过流式细胞术测量淋巴细胞计数,通过酶联免疫吸附试验(ELISA)分别检测细胞因子水平。采用 Kaplan-Meier 法计算无进展生存期(PFS)曲线,采用对数秩检验评估差异。

结果

本研究共纳入 201 名年龄≥65 岁的老年肺癌患者。最常见的 irAE 是间质性肺炎、皮肤毒性和甲状腺功能减退症,发生率分别为 17.2%、16.1%和 5.6%。ROC 显示,G-8 可预测 65-71 岁患者(≥G2 irAE:AUC=0.757,p<0.001;≥G3 irAE:AUC=0.862,p<0.001)发生 irAE,但对年龄≥71 岁患者则不行。NLR、LMR、PNI、高血压和糖尿病与 irAE 相关。较低的 CD4+T 细胞和 B 细胞以及较低的 IL-10 水平与 irAE 的发生相关。

结论

本研究证实了 G-8 对预测老年患者 irAE 的准确性,同时还确定了老年肺癌患者 irAE 的几个预测因素。

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