The objective of this study was to identify potential predictors of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitor therapy among serum indexes, case data, and liquid biopsy results. We retrospectively analyzed 418 patients treated with anti-programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) inhibitors from January 2018 to May 2022 in our cancer center. We identified factors that correlated with the occurrence of irAEs and evaluated associations between irAEs and anti-PD-1/PD-L1 inhibitor responses. The incidence of irAEs was 42.1%, and pneumonitis (9.1%), thyroid toxicity (9.1%), cardiotoxicity (8.1%), and dermatologic toxicity (6.9%) were the four most common irAEs. Multivariate logistic analysis identified female sex, antibiotic use, higher post-treatment neutrophil-to-lymphocyte ratio (NLR), and higher baseline circulating tumor cell (CTC) level, as predictive biomarkers for the occurrence of irAEs. A lower baseline prognostic nutritional index (PNI), body mass index (BMI) ≥ 25 kg/m2, and higher post-treatment lactate dehydrogenase (LDH) level were predictive factors for more severe irAEs (higher severity grade). Patients without irAEs had better overall survival than those with irAEs. Specifically, pneumonitis and cardiotoxicity were found to be significant predictors of poor prognosis in the irAE subgroup with different organ-related irAEs. Low-dose steroid (dexamethasone 10 mg) treatment had no significant effect on outcomes. Gender, antibiotic use, post-treatment NLR, and baseline CTC level are potential predictive biomarkers of irAEs, while baseline PNI, BMI, and post-treatment LDH may predict the severity of irAEs. The predictive effect of irAE occurrence on survival benefit may depend on the type of irAE.

中文翻译：

---

接受免疫检查点抑制剂治疗的癌症患者中免疫相关不良事件的预测生物标志物

本研究的目的是在血清指标、病例数据和液体活检结果中确定接受免疫检查点抑制剂治疗的癌症患者免疫相关不良事件 (irAE) 的潜在预测因素。我们回顾性分析了2018年1月至2022年5月在我们癌症中心接受抗程序性细胞死亡1（PD-1）/PD-1配体（PD-L1）抑制剂治疗的418名患者。我们确定了与 irAE 发生相关的因素，并评估了 irAE 与抗 PD-1/PD-L1 抑制剂反应之间的关联。irAE 的发生率为 42.1%，其中肺炎（9.1%）、甲状腺毒性（9.1%）、心脏毒性（8.1%）和皮肤毒性（6.9%）是四种最常见的 irAE。多变量逻辑分析确定女性、抗生素使用、治疗后较高的中性粒细胞与淋巴细胞比率 (NLR) 和较高的基线循环肿瘤细胞 (CTC) 水平作为 irAE 发生的预测生物标志物。较低的基线预后营养指数 (PNI)、体重指数 (BMI) ≥ 25 kg/m2 和较高的治疗后乳酸脱氢酶 (LDH) 水平是更严重的 irAE（更高严重程度）的预测因素。没有 irAE 的患者比有 irAE 的患者有更好的总生存期。具体而言，发现肺炎和心脏毒性是具有不同器官相关 irAE 的 irAE 亚组预后不良的重要预测因子。低剂量类固醇（地塞米松 10 mg）治疗对结果没有显着影响。性别、抗生素使用、治疗后 NLR 和基线 CTC 水平是 irAE 的潜在预测生物标志物，而基线 PNI、BMI 和治疗后 LDH 可以预测 irAE 的严重程度。irAE 发生对生存获益的预测作用可能取决于 irAE 的类型。