NSCLC患者使用ICIs时发生免疫相关不良事件的危险因素及与疗效的关系  

The risk factor analysis for immune-related adverse events in non-small cell lung cancer patients treated with immune checkpoint inhibitors and their relationship to effectiveness

作　　者：徐金慧 续广娟 段露芬 刘凯丽 周琴[1] 孙坚彤[1] 丁信园[1] XU Jinhui;XU Guangjuan;DUAN Lufen;LIU Kaili;ZHOU Qin;SUN Jiantong;DING Xinyuan(Department of Pharmacy,the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital,Suzhou 215002,China;Department of Oncology,the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital,Suzhou 215002,China)

机构地区：[1]南京医科大学附属苏州医院/苏州市立医院药剂科,215002 [2]南京医科大学附属苏州医院/苏州市立医院肿瘤科,215002

出　　处：《天津医药》2023年第2期207-212,共6页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(81902320);吴阶平医学基金会临床科研专项资助基金(320.6750.2020-12-69);苏州市科技发展计划(SKJYD2021170);江苏省药学会恒瑞医院药学基金(H202114)。

摘　　要：目的 探究非小细胞肺癌(NSCLC)患者使用免疫检查点抑制剂(ICIs)时发生免疫相关不良事件(irAEs)的独立危险因素,并评估irAEs与临床疗效的关系。方法 回顾性纳入162例接受ICIs治疗的NSCLC患者,收集人口学、临床特征和外周血液生物标志物,采用Logistic回归分析irAEs的独立危险因素,并评估irAEs与客观有效率(ORR)、无进展生存期(PFS)和总生存期(OS)的关系。结果 83例患者发生了130例次irAEs,12例患者发生了严重的irAEs。较常见irAEs为皮肤毒性(34.6%)和免疫相关性肺炎(21.5%),严重irAEs中发生率最高者为免疫相关性肺炎(5.4%)。基线绝对淋巴细胞(ALC)水平增高是全体患者发生irAEs的独立危险因素(OR=3.195,95%CI:1.341~7.610,P=0.009),同样也是ICIs单药治疗患者(OR=5.613,95%CI:1.109~28.411,P=0.037)、ICIs联合化疗患者(OR=2.901,95%CI:1.102~7.633,P=0.031)发生irAEs的独立危险因素。受试者工作特征曲线显示ALC预测是否发生irAEs曲线下面积为0.713(95%CI:0.633~0.792),最佳临界值为1.25×10^(9)/L,敏感度、特异度分别为71.1%和62.0%。与无irAEs患者相比,有irAEs患者的ORR更高(38.6%vs. 21.5%,χ^(2)=5.567,P<0.05),中位PFS更长(329 d vs. 206 d,Log-rankχ^(2)=5.256,P<0.05),中位OS也更长(690 d vs. 434 d,Log-rankχ^(2)=4.670,P<0.05)。结论 基线ALC水平增高是NSCLC患者发生irAEs的独立危险因素,irAEs的发生与患者ORR、PFS和OS的改善有关。Objective To explore risk factors for immune-related adverse events(irAEs) in patients with non-small cell lung cancer(NSCLC) treated with immune checkpoint inhibitors(ICIs) and to investigate the relationship between irAEs and effectiveness.Methods A total of 162 NSCLC patients treated with ICIs were retrospectively enrolled.Baseline demographic and clinical characteristics,peripheral blood biomarkers and irAEs were collected and evaluated.Logistic regression analysis was performed to identify risk factors of irAEs.The relationships between irAEs,overall response rate(ORR),progression-free survival(PFS) and overall survival(OS) were also evaluated.Results Eighty-three patients experienced 130 times of irAEs and 12 patients had severe irAEs.The most observed irAEs were skin toxicity(34.6%),immune-related pneumonitis(21.5%),and the most common severe irAEs was immune-related pneumonitis(5.4%).A higher pretreatment absolute lymphocyte count(ALC) was an independent risk factor for irAEs in all patients(OR=3.195,95%CI:1.341-7.610,P=0.009).They were also independent risk factors for irAEs in patients treated with ICIs only(OR=5.613,95%CI:1.109-28.411,P=0.037) and in patients treated with chemoimmunotherapy(OR=2.901,95%CI:1.102-7.633,P=0.031).Receiver operating characteristic curve analyses revealed that the ALC level yielded an AUC of 0.713(95%CI:0.633-0.792) with 71.1% sensitivity and 62.0% specificity at the cut-off level of 1.25×10^(9)/L to predict the risk of irAEs.Compared with the non-irAEs group,the objective response rate(ORR) was higher in the irAEs group(38.6% vs.21.5%,χ^(2)=5.567,P <0.05).Patients in the irAEs group had a longer PFS(329 d vs.206 d,Log-rank χ^(2)=5.256,P <0.05) as well as OS(690 d vs.434 d;Log-rank χ^(2)=4.670,P <0.05).Conclusion An increased baseline ALC level is identified as an independent risk factor for the development of irAEs in NSCLC patients.Moreover,the occurrence of irAEs is significantly associated with the improvement of ORR,PFS and OS.

关 键 词：癌 非小细胞肺 免疫检查点抑制剂 淋巴细胞 存活率分析 免疫相关不良事件 

分 类 号：R734.2[医药卫生—肿瘤]