摘要
目的探讨恶性肿瘤患者应用替雷利珠单抗治疗后免疫相关不良事件(irAE)的发生情况、影响因素及其预测生物标志物。方法收集上海交通大学医学院附属第九人民医院2020年6月至2023年6月应用替雷利珠单抗治疗至少1个周期恶性肿瘤成年患者的电子病历,对irAE发生情况和临床特征进行回顾性分析。按照患者是否发生irAE,将患者分为irAE组和非irAE组。比较2组患者的临床特征和相关生物标志物水平。采用多因素logistic回归方法分析患者发生irAE的危险因素。对有预测意义的生物标志物,采用受试者工作特征(ROC)曲线分析其预测irAE发生风险的折点。结果共纳入患者107例,男性81例(75.7%),女性26例(24.3%),年龄(61±15)岁,其中25例(23.4%)判定为替雷利珠单抗相关irAE,6例(5.6%)严重程度≥3级。25例患者共发生28例次irAE,包括甲状腺功能异常9例次、免疫相关性肠炎4例次、皮疹4例次、免疫相关性肺炎3例次、肾损伤3例次、肝损伤3例次、免疫相关性肌炎1例次、高血压1例次。替雷利珠单抗开始治疗至irAE发生的中位治疗周期为3(1,5)个。25例患者irAE经停药和/或糖皮质激素及对症治疗后均好转,无因irAE死亡病例。多因素logistic回归分析结果显示基线中性粒细胞与淋巴细胞比值(NLR)高是保护因素[比值比(OR)=0.453,95%置信区间(CI):0.279~0.735,P=0.001],而基线血小板与淋巴细胞比值(PLR)高是危险因素(OR=1.006,95%CI:1.002~1.011,P=0.008)。ROC曲线分析结果显示,基线NLR和PLR预测irAE发生的折点分别为1.58(敏感度为0.988,特异度为0.644)和159.40(敏感度为0.800,特异度为0.524)。结论替雷利珠单抗治疗成人恶性肿瘤的irAE发生率为23.4%,以甲状腺功能异常最为常见,免疫相关性肠炎、皮疹、肺炎、肾损伤和肝损伤也值得关注。基线NLR和PLR可能作为预测irAE发生的生物标志物。
Objective To explore the occurrence,influencing factors,and predictive biomarkers of immune⁃related adverse events(irAEs)in malignant tumor patients treated with tislelizumab.Methods The electronic medical records of adult patients with malignant tumors,who received tislelizumab for at least one cycle from June 2020 to June 2023 at Shanghai Ninth People′s Hospital,Shanghai Jiao Tong University School of Medicine,were collected,and the occurrence and clinical characteristics of irAEs were retrospec⁃tively analyzed.Patients were divided into irAEs group and non⁃irAEs group according to whether they had irAEs.The clinical characteristics and detection value of biomarkers in patients of the 2 groups were com⁃pared.Multivariate logistic regression was used to analyze the risk factors of irAEs in patients.The receiver operating characteristic(ROC)curve was used to find the cutoff point of the biomarkers for predicting the irAEs.Results A total of 107 patients were entered,including 81 males(75.7%)and 26 females(24.3%),aged(61±15)years.Among them,25 patients(23.4%)were diagnosed with tislelizumab⁃related irAEs,of which 6 patients(5.6%)had irAEs with a severity of grade 3 and above.A total of 28 irAEs occurred in the 25 patients,including 9 cases of thyroid dysfunction,4 cases of immune⁃related enteritis,4 cases of rashes,3 cases of immune⁃related pneumonitis,3 cases of kidney injury,3 cases of liver injury,1 case of immune⁃related myositis,and 1 case of hypertension.The median treatment cycle from the start of tislelizumab to the occurrence of irAEs was 3(1,5)cycles.After discontinuation of tislelizumab and/or glucocorticoids and symptomatic treatments,all 25 patients were improved.No deaths occurred due to irAEs.The results of multi⁃variate logistic regression analysis showed that a high neutrophil-to-lymphocyte ratio(NLP)at baseline was a protective factor for irAEs[odds ratio(OR)=0.453,95%confidence interval(CI):0.279-0.735,P=0.001],while a high platelet⁃to⁃lymphocyte ratio(PLR)at baseline wa
作者
诸慧
原永芳
徐影
Zhu Hui;Yuan Yongfang;Xu Ying(Department of Pharmacy,Shanghai Ninth People′s Hospital,Shanghai JiaoTong University School of Medi-cine,Shanghai 200011,China)
出处
《药物不良反应杂志》
CSCD
2024年第1期18-24,共7页
Adverse Drug Reactions Journal
