替雷利珠单抗致恶性肿瘤患者多器官免疫相关不良反应的临床研究

Clinical study on multi-organ immune-related adverse events induced by tislelizumab in patients with malignant tumors

摘要:

目的 探讨替雷利珠单抗致恶性肿瘤患者多器官免疫相关不良反应（irAEs）的发生情况和危险因素。方法 回顾性分析2022年10月—2024年10月在中国人民解放军联勤保障部队第九六一医院肿瘤科接受替雷利珠单抗治疗的149例恶性肿瘤患者的临床资料。将发生irAEs的患者设为观察组（43例），未发生irAEs的患者设为对照组（106例）。对比两组临床资料。通过多因素一般Logistic回归模型分析irAEs的危险因素，并采用受试者工作特征（ROC）曲线评估诊断效能。结果 irAEs发生率为28.86%（43/149）。观察组肿瘤类型为非小细胞肺癌、联合化疗药物、病程≥ 1年的比例均高于对照组（P <0.05），NLR水平低于对照组（P <0.05），PLR水平高于对照组（P <0.05）。两组性别构成、年龄、体质量指数、基础疾病、吸烟史、饮酒史、TNM分期、嗜酸粒细胞计数和绝对淋巴细胞计数水平比较，差异均无统计学意义（P >0.05）。多因素一般Logistic回归分析，结果显示：肿瘤类型为非小细胞肺癌［O^R =9.915（95% CI：1.230，79.904）］、联合化疗药物［O^R =15.786（95% CI：1.515，164.457）］、病程≥ 1年［O^R =6.702（95% CI：1.513，29.682）］、中性粒细胞与淋巴细胞比值降低［O^R =0.038（95% CI：0.006，0.260）］和血小板与淋巴细胞比值升高［O^R =1.093（95% CI：1.046，1.143）］均是发生irAEs的危险因素（P <0.05）。ROC曲线结果显示，基于多因素一般Logistic回归模型诊断，敏感性为93.0%（95% CI：0.809，0.985），特异性为92.5%（95% CI：0.857，0.967）。结论 替雷利珠单抗治疗恶性肿瘤患者时，irAEs发生与肿瘤类型、治疗方案及特定免疫指标密切相关。

Abstract:

Objective To investigate the incidence and risk factors of multi-organ immune-related adverse events (irAEs) induced by tislelizumab in patients with malignant tumors.Methods A total of 149 patients with malignant tumor who received tislelizumab treatment in the Department of Oncology from October 2022 to October 2024 were included. Patients who developed irAEs were assigned to the observation group (n =43), while those who did not develop irAEs were assigned to the control group (n =106). A comparison of clinical traits was made between the two groups. Multivariable Logistic regression analysis was used to identify factors influencing the occurrence of irAEs, and the diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis.Results The incidence of irAEs was 28.86% (43/149). In the observation group, the proportions of patients with non-small cell lung cancer, those receiving combination therapy, and those with a disease course ≥ 1 year were all significantly higher than those in the control group (P < 0.05). Additionally, the neutrophil-to-lymphocyte ratio (NLR) was significantly lower (P <0.05), while the platelet-to-lymphocyte ratio (PLR) was significantly higher in the observation group compared to those in the control group (P < 0.05). There was no statistically significant difference between the two groups in terms of sex distribution, age, BMI, comorbidities, smoking history, alcohol consumption history, TNM stage, EOS, and ALC (P > 0.05). Multivariable Logistic regression analysis revealed that non-small cell lung cancer [O^R = 9.915 (95% CI: 1.230, 79.904) ], combination therapy [O^R = 15.786 (95% CI: 1.515, 164.457) ], disease duration ≥ 1 year [O^R = 6.702 (95% CI: 1.513, 29.682) ], decreased NLR [O^R = 0.038 (95% CI: 0.006, 0.260) ], and increased PLR [O^R = 1.093 (95% CI: 1.046, 1.143) ] were all independent risk factors for the development of irAEs (P < 0.05). ROC curve analysis based on the multivariable Logistic regression model demonstrated a sensitivity of 93.0% (95% CI: 0.809, 0.985) and a specificity of 92.5% (95% CI: 0.857, 0.967) for predicting the occurrence of irAEs.Conclusion The occurrence of irAEs in patients with malignant tumors treated with tislelizumab is closely associated with tumor type, treatment regimen, and specific immune-related biomarkers.