肺癌患者免疫检查点抑制剂相关肺炎的危险因素及临床特点-东南大学学报医学版

肺癌患者免疫检查点抑制剂相关肺炎的危险因素及临床特点

单位：南京大学医学院附属金陵医院呼吸与危重症医学科, 江苏南京 210002

分类号：R734.2

出版年·卷·期（页码）：2024·43·第四期（516-522）

摘要：

目的: 分析肺癌患者免疫检查点抑制剂(ICIs)相关肺炎(CIP)的危险因素及临床特点。方法: 选择2021年7月至2022年12月在南京大学医学院附属金陵医院接受ICIs治疗的肺癌患者为研究对象,根据是否发生CIP分为CIP组和非CIP组,绘制受试者工作特征(ROC)曲线确定连续变量预测CIP发生的最佳临界值,采用多因素 Logistic 回归分析肺癌患者发生CIP的危险因素,多因素Cox回归分析CIP患者无进展生存期(PFS)的影响因素。结果: 纳入的307例接受ICIs治疗的肺癌患者中,38例(12.38%)患者发生了CIP,其中1例患者出现与CIP相关的死亡。多因素 Logistic 回归分析结果显示,慢性阻塞性肺疾病、低基线淋巴细胞计数(临界值1.265×10⁹L^-1)和高基线嗜酸粒细胞计数(临界值0.245×10⁹L^-1)是肺癌患者发生CIP的独立危险因素(P<0.05)。多因素Cox回归显示,吸烟史和严重程度是CIP患者PFS的影响因素(P<0.05)。结论: 慢性阻塞性肺疾病、低基线淋巴细胞计数、高基线嗜酸粒细胞计数与肺癌患者CIP风险增加独立相关。有吸烟史和临床分级高的CIP患者免疫疗效不佳。

Objective: To retrospectively analyze the clinical characteristics and risk factors of immune checkpoint inhibitor-related pneumonitis(CIP) in lung cancer patients. Methods: Lung cancer patients who were treated with immune checkpoint inhibitors(ICIs) in Jinling Hospital from July 2021 to December 2022 were selected for the study. They were divided into CIP group and non-CIP group according to whether or not CIP occurred. The receiver operating characteristic(ROC) curve determined the optimal cut-off value of continuous variables for predicting CIP in lung cancer patients. The risk factors for CIP in lung cancer patients were analyzed by multivariate Logistic regression. Multivariate Cox regression was used to analyze the factors affecting progression-free survival(PFS) in patients with CIP. Results: Of the 307 lung cancer patients treated with ICIs included, 38(12.38%) patients developed CIP, and one of them experienced a CIP-related death. The results of multivariate Logistic regression analysis showed that chronic obstructive pulmonary disease, low baseline lymphocyte counts and high baseline eosinophil counts were independent risk factors for the development of CIP in lung cancer patients(P<0.05). In patients with CIP, multivariate Cox regression showed that smoking history and severe CIP were influential factors for PFS(P<0.05). Conclusion: Chronic obstructive pulmonary disease, low baseline lymphocyte counts and high baseline eosinophil counts are independently associated with an increased risk of CIP in patients with lung cancer. CIP patients with a history of smoking and high clonical grade have poor immunotherapy outcomes.

参考文献：

[1] SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[2] VADDEPALLY R K,KHAREL P,PANDEY R,et al.Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence[J].Cancers (Basel),2020,12(3):738.
[3] RAMOS-CASALS M,BRAHMER J R,CALLAHAN M K,et al.Immune-related adverse events of checkpoint inhibitors[J].Nat Rev Dis Primers,2020,6(1):38.
[4] SURESH K,NAIDOO J,LIN C T,et al.Immune checkpoint immunotherapy for non-small cell lung cancer:benefits and pulmonary toxicities[J].Chest,2018,154(6):1416-1423.
[5] SU Q,ZHU E C,WU J B,et al.Risk of pneumonitis and pneumonia associated with immune checkpoint inhibitors for solid tumors:a systematic review and meta-analysis[J].Front Immunol,2019,10:108.
[6] EL OSTA B,HU F,SADEK R,et al.Not all immune-checkpoint inhibitors are created equal:meta-analysis and systematic review of immune-related adverse events in cancer trials[J].Crit Rev Oncol Hematol,2017,119:1-12.
[7] DENG H,DENG J,LIN X,et al.A risk-scoring model for severe checkpoint inhibitor-related pneumonitis:a case-control study[J].Clin Drug Investig,2023,43(5):347-357.
[8] ATCHLEY W T,ALVAREZ C,SAXENA-BEEM S,et al.Immune checkpoint inhibitor-related pneumonitis in lung cancer:real-world incidence,risk factors,and management practices across six health care centers in North Carolina[J].Chest,2021,160(2):731-742.
[9] PAVAN A,CALVETTI L,DAL MASO A,et al.Peripheral blood markers identify risk of immune-related toxicity in advanced non-small cell lung cancer treated with immune-checkpoint inhibitors[J].Oncologist,2019,24(8):1128-1136.
[10] SHAVERDIAN N,LISBERG A E,BORNAZYAN K,et al.Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer:a secondary analysis of the KEYNOTE-001 phase 1 trial[J].Lancet Oncol,2017,18(7):895-903.
[11] LIN X,DENG H,YANG Y,et al.Peripheral blood biomarkers for early diagnosis,severity,and prognosis of checkpoint inhibitor-related pneumonitis in patients with lung cancer[J].Front Oncol,2021,11:698832.
[12] MüLLER K M.Histological classification and histogenesis of lung cancer[J].Eur J Respir Dis,1984,65(1):4-19.
[13] 中华医学会呼吸病学分会肺癌学组.免疫检查点抑制剂相关肺炎诊治专家共识[J].中华结核和呼吸杂志,2019,42(11):820-825.
[14] 田雨,陆元花,赵沛妍,等.肺癌免疫治疗相关肺炎生物标志物的研究进展[J].现代医学,2024,52(3):492-498.
[15] NISHINO M,RAMAIYA N H,AWAD M M,et al.PD-1 inhibitor-related pneumonitis in advanced cancer patients:radiographic patterns and clinical course[J].Clin Cancer Res,2016,22(24):6051-6060.
[16] NAIDOO J,WANG X,WOO K M,et al.Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy[J].J Clin Oncol,2017,35(7):709-717.
[17] WANG H,ZHAO Y,ZHANG X,et al.Clinical characteristics and management of immune checkpoint inhibitor-related pneumonitis:a single-institution retrospective study[J].Cancer Med,2021,10(1):188-198.
[18] 王汉萍,郭潇潇,周佳鑫,等.免疫检查点抑制剂相关肺炎的临床诊治建议[J].中国肺癌杂志,2019,22(10):621-626.
[19] DE VELASCO G,JE Y,BOSSō D,et al.Comprehensive meta-analysis of key immune-related adverse events from CTLA-4 and PD-1/PD-L1 inhibitors in cancer patients[J].Cancer Immunol Res,2017,5(4):312-318.
[20] CHAO Y,ZHOU J,HSU S,et al.Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer[J].Transl Lung Cancer Res,2022,11(2):295-306.
[21] BENJAMIN J T,PLOSA E J,SUCRE J M,et al.Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD[J].J Clin Invest,2021,131(1):e139481.
[22] BRIGHTLING C,GREENING N.Airway inflammation in COPD:progress to precision medicine[J].Eur Respir J,2019,54(2):1900651.
[23] CARAMORI G,RUGGERI P,MUMBY S,et al.Molecular links between COPD and lung cancer:new targets for drug discovery?[J].Expert Opin Ther Targets,2019,23(6):539-553.
[24] BAI R,CHEN N,CHEN X,et al.Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events[J].Cancer Biol Med,2021,18(4):1118-1133.
[25] GRIVENNIKOV S I,GRETEN F R,KARIN M.Immunity,inflammation,and cancer[J].Cell,2010,140(6):883-899.
[26] WU Y,LI D,WU M,et al.Peripheral absolute eosinophil count identifies the risk of serious immune-related adverse events in non-small cell lung cancer[J].Front Oncol,2022,12:1004663.
[27] MA Y,MA X,WANG J,et al.Absolute eosinophil count may be an optimal peripheral blood marker to identify the risk of immune-related adverse events in advanced malignant tumors treated with PD-1/PD-L1 inhibitors:a retrospective analysis[J].World J Surg Oncol,2022,20(1):242.
[28] CALIMAN E,FANCELLI S,OTTANELLI C,et al.Absolute eosinophil count predicts clinical outcomes and toxicity in non-small cell lung cancer patients treated with immunotherapy[J].Cancer Treat Res Commun,2022,32:100603.
[29] SIMON S C S,UTIKAL J,UMANSKY V.Opposing roles of eosinophils in cancer[J].Cancer Immunol Immunother,2019,68(5):823-833.
[30] CHU X,ZHAO J,ZHOU J,et al.Association of baseline peripheral-blood eosinophil count with immune checkpoint inhibitor-related pneumonitis and clinical outcomes in patients with non-small cell lung cancer receiving immune checkpoint inhibitors[J].Lung Cancer,2020,150:76-82.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录