摘要
目的探讨免疫检查点抑制剂(ICIs)治疗非小细胞肺癌(NSCLC)引起皮肤免疫相关不良反应(irAE)的临床特征及预后。方法本研究为回顾性队列研究。纳入2019年1月至2021年12月在上海交通大学医学院附属瑞金医院接受ICIs治疗后出现皮肤irAE的NSCLC患者34例。对所有患者进行随访,直至死亡。收集所有患者的临床资料,包括性别、年龄、吸烟史、美国东部肿瘤协作组功能状态评分、病理类型、驱动基因类型、细胞程序性死亡-配体1表达、实验室检验结果、皮肤irAE情况、治疗方案。根据美国国家癌症研究所发布的第5版不良反应事件通用术语标准对皮肤irAE的严重程度进行分级,比较不同严重程度皮肤irAE患者的实验室检验结果。比较不同类型皮肤irAE患者的无进展生存期(PFS)。结果34例NSCLC患者中G1~G4级皮肤irAE均有发生,分别有26例(76.5%)、6例(17.6%)、1例(2.9%)、1例(2.9%)。类型包括斑丘疹、瘙痒症、反应性皮肤毛细血管增生症(RCCEP)、白癜风、苔藓样皮炎、皮肤色素沉着、大疱性皮损和重叠型重症多形红斑型药疹-中毒性表皮坏死松解症(SJS-TEN)。G2级及以上组中性粒细胞数高于G1组,差异有统计学意义[(6.15±2.63)×10^(9)/L比(4.06±1.79)×10^(9)/L,t=2.58,P<0.05]。单纯表现为RCCEP、斑丘疹、瘙痒症患者的PFS分别为(7.94±3.49)个月、(14.21±9.59)个月、(17.95±11.88)个月,差异有统计学意义(F=2.54,P=0.015)。接受全身和(或)外用糖皮质激素治疗的患者皮疹均有好转,只有3例(8.8%)后续暂停ICIs使用。暂停ICIs使用患者的PFS与继续使用ICIs患者的PFS比较,差异无统计学意义[(10.81±4.01)个月比(12.74±9.07)个月;t=0.36,P=0.720]。因皮肤irAE接受全身糖皮质激素治疗患者与未使用糖皮质激素患者的PFS比较差异无统计学意义[(11.35±7.15)个月比(13.43±9.76)个月;t=0.68,P=0.504]。结论ICIs治疗NSCLC可引起斑丘疹、瘙痒症、RCCEP、白癜风、皮肤色素沉着、大疱性皮损等不同类型的皮肤irAE。严重程度分级越高,中性粒细胞水平越高。发生斑丘疹、瘙痒症、RCCEP患者中,瘙痒症患者PFS最长。
Objective To investigate the clinical characteristics and prognosis of cutaneous immune-related adverse events(irAEs)in non-small cell lung cancer patients(NSCLC)treated with immune checkpoint inhibitors(ICIs).Methods It was a retrospective cohort study involving 34 NSCLC patients treated with ICIs from January 2019 to December 2021 in Ruijin Hospital,Shanghai Jiaotong University School of Medicine.All patients were followed up until death.Clinical data were collected from all patients,including gender,age,smoking history,Eastern Cooperative Oncology Group(ECOG)functional status score,pathological type,driver gene type,programmed cell death ligand 1(PD-L1)expression,laboratory test results,cutaneous irAEs and treatment regimen.The severity of cutaneous irAEs was graded according to the 5th edition of Common Terminology Criteria for Adverse Events(CTCAE)published by the National Cancer Institute.Laboratory test results in NSCLC patients with varying degree of cutaneous irAEs,and the progression-free survival(PFS)in them with varying types of cutaneous irAEs were compared.Results G1-G4 cutaneous irAEs were all observed in 34 recruited NSCLC patients treated with ICIs,including 26(76.5%),6(17.6%),1(2.9%),and 1(2.9%)case of G1,G2,G3 and G4,respectively.Reported cutaneous irAEs included maculopapular,pruritus,reactive cutaneous capillary endothelial proliferation(RCCEP),vitiligo,lichenoid dermatitis,skin pigmentation,bullous lesions,and Stevens-Johnson syndrome/toxic epidermal necrolysis(SJS/TEN).The number of neutrophils in NSCLC patients with G2 and above cutaneous irAEs was significantly higher than those with G1([6.15±2.63]×10^(9)/L vs[4.06±1.79]×10^(9)/L,t=2.58,P<0.05).The PFS of NSCLC patients with maculopapules,RCCEP and pruritus was significantly different([14.21±9.59]months vs[7.94±3.49]months vs[17.95±11.88]months,F=2.54,P=0.015).All patients who received systemic and/or topical glucocorticoids had improvement in rash,and ICIs were withdrawn in only 3(8.8%)patients.There was no significant difference in the PFS of NSCLC patients with the withdrawal of ICIs or not([10.81±4.01]months vs[12.74±9.07]months;t=0.36,P=0.720),nor as that between NSCLC patients treated with systemic glucocorticoid therapy due to cutaneous irAEs or not([11.35±7.15]months vs[13.43±9.76]months;t=0.68,P=0.504).Conclusions The treatment of ICIs can cause different types of cutaneous irAEs in NSCLC patients,including maculopapular eruption,pruritus,RCCEP,bullous rash,vitiligo,skin pigmentation,etc.The higher the severity of cutaneous irAEs,the higher the neutrophil level.The longest PFS is observed in ICI-treated NSCLC patients with pruritus.
作者
张琼
胡维婷
王晓斐
Zhang Qiong;Hu Weiting;Wang Xiaofei(Department of Pulmonary and Critical Care Medicine,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China;Department of Pulmonary and Critical Care Medicine,People′s Hospital of Wuwei,Wuwei 733000,China)
出处
《国际呼吸杂志》
2023年第7期783-788,共6页
International Journal of Respiration
基金
吴阶平医学基金会临床科研专项资金基金(320.6750.19088-97)。
作者简介
通信作者:王晓斐,Email:wxf11524@rjh.com.cn。
