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免疫检查点抑制剂联合铂类药物化疗治疗非小细胞肺癌患者发生免疫相关不良事件的危险因素:一项多中心回顾性研究。

Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study.

机构信息

Department of Pharmacy, National Hospital Organization Beppu Medical Center, 473 Uchikamado, Beppu, Oita, 874-0011, Japan.

Department of Pharmacy, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.

出版信息

Cancer Immunol Immunother. 2023 Jul;72(7):2169-2178. doi: 10.1007/s00262-023-03408-4. Epub 2023 Feb 27.

Abstract

PURPOSE

Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy.

METHODS

This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors.

RESULTS

Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence.

CONCLUSION

Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.

摘要

目的

免疫检查点抑制剂(ICI)为非小细胞肺癌(NSCLC)的治疗开创了新纪元。然而,它们存在免疫相关不良反应(irAEs)的风险。最近,许多研究都针对 irAEs 的预测因素进行了研究,但尚无仅针对 ICI 联合铂类药物的诱导免疫化疗的研究报告。本研究旨在确定 NSCLC 患者接受 ICI 联合铂类药物诱导免疫化疗时发生 irAEs 的危险因素,仅关注联合治疗期间,不包括 ICI 维持治疗期间。

方法

本回顾性研究纳入了 2018 年 12 月至 2021 年 3 月间在 14 家医院接受 ICI 联合铂类化疗治疗的 315 例 NSCLC 患者。采用逻辑回归分析探讨预测因素。

结果

50 例患者(15.9%)发生 irAEs。多因素分析显示,鳞状细胞癌(P=0.021;优势比[OR]:2.30;95%置信区间[Cl]:1.14-4.65)、抗程序性死亡 1 抗体(抗-PD-1)联合抗细胞毒性 T 淋巴细胞相关抗原 4 抗体(抗-CTLA-4)方案(P<0.01;OR:22.10;95% Cl:5.60-87.20)和中性粒细胞与淋巴细胞比值(NLR)<3(P<0.01;OR:2.91;95% Cl:1.35-6.27)是 irAEs 发生的独立预测因素。

结论

鳞状细胞癌、抗-PD-1 联合抗-CTLA-4 方案和 NLR<3 可能是 NSCLC 患者接受诱导免疫化疗时发生 irAEs 的预测因素。通过关注这些因素患者发生 irAEs 的潜在风险,可以及早进行适当的管理。

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