免疫检查点抑制药相关甲状腺功能障碍的预测及疗效预后临床研究  

Clinical study on prediction and prognosis of thyroid dysfunction related to immune checkpoint inhibitor therapy

作　　者：刘雅娟[1] 莫丽钦 张晓诺 曹莹 张珍[1] 张媛慧[2] LIU Ya-juan;MO Li-qin;ZHANG Xiao-nuo;CAO Ying;ZHANG Zhen;ZHANG Yuan-hui(The Third Department of Internal Medicine,Hangzhou Cancer Hospital,Hangzhou 310002,Zhejiang Province,China;The Second Department of Internal Medicine,Hangzhou Cancer Hospital,Hangzhou 310002,Zhejiang Province,China)

机构地区：[1]杭州市肿瘤医院内三科,浙江杭州310002 [2]杭州市肿瘤医院内二科,浙江杭州310002

出　　处：《中国临床药理学杂志》2022年第22期2668-2673,共6页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省医药卫生科技计划基金资助项目(2020KY492);浙江省医学会临床科研基金资助项目(2018ZYC-A04);浙江省中医药科技计划基金资助项目(2020ZB034)。

摘　　要：目的分析恶性肿瘤患者接受免疫检查点抑制药后免疫相关性甲状腺功能障碍的发生情况和相关因素与生存预后的关系。方法回顾性分析2019年4月-2022年4月在杭州市肿瘤医院接受免疫检查点抑制药治疗[程序性死亡受体1(PD-1)单抗或细胞程序性死亡-配体1(PD-L1)单抗],符合纳入排除标准的恶性肿瘤患者的临床资料。根据患者甲状腺激素水平情况分成甲状腺功能障碍组(irT组)和甲状腺功能正常组(非irT组),对比2组之间临床特征及甲状腺激素的差异,分析发生甲状腺功能障碍的相关因素以及比较2组患者无进展生存时间(PFS)的差异。结果入组91例接受免疫检查点抑制药治疗的恶性肿瘤患者。28例(30.8%)发生了免疫相关的甲状腺功能障碍,其中发生亚临床甲状腺功能亢进的患者有8例(8.8%),临床甲状腺功能亢进的患者有0例(0.0%);亚临床甲状腺功能减退的患者有12例(13.2%),临床甲状腺功能减退的患者有8例(8.8%)。多因素Logistic回归分析发现,基线促甲状腺激素(TSH)水平越高,甲状腺功能减退的发生率越高(OR=2.068,95%CI=1.282~3.334;P<0.01)。使用受试者工作特征曲线分析发现,基线TSH水平>2.897 mIU·L^(-1)(特异度:91.53%,敏感度:50.00%)能较好的预测患者甲状腺功能减退(P<0.05)。在总体人群和肺癌人群中,免疫检查点抑制药治疗用药后,与甲状腺功能正常组相比,发生甲状腺功能异常的患者有更长的PFS(HR=0.542,95%CI=0.292~1.007,P<0.05及HR=0.192,95%CI=0.045~0.813,P<0.05),均有统计学意义。结论使用免疫检查点抑制药后,基线TSH水平与甲状腺功能减退有关,用药后发生甲状腺功能障碍提示更长的生存获益。Objective To analyze the incidence and related factors of immune related thyroid dysfunction and its relationship with survival and prognosis in patients with malignant tumors after receiving immune checkpoint inhibitors.Methods The clinical data of patients with malignant tumors who received immune checkpoint inhibitors[programmed death receptor 1(PD-1)monoclonal antibody or programmed cell death ligand 1(PD-L1)monoclonal antibody]in the Hangzhou cancer hospital from April 2019 to April 2022 and met the inclusion and exclusion criteria were retrospectively analyzed.According to the thyroid hormone level,the patients were divided into thyroid dysfunction group(irT group)and normal thyroid function group(nonirT group).The clinical characteristics and thyroid hormone differences between the two groups were compared,the related factors of thyroid dysfunction were analyzed,and the progression free survival(PFS)differences between the two groups were compared.Results Ninety-one patients with malignant tumors who received immune checkpoint inhibitors were enrolled.Among them,28 patients(30.8%)had immune related thyroid dysfunction,including 8 patients(8.8%)with subclinical hyperthyroidism and 0 patients(0.0%)with clinical hyperthyroidism.There were 12 patients(13.2%)with subclinical hypothyroidism and 8 patients(8.8%)with clinical hypothyroidism.Multivariate logistic regression analysis showed that the higher the baseline TSH level,the higher the incidence of hypothyroidism(OR=2.068,95%CI,1.282-3.334;P<0.01).Receiver operating characteristic curve analysis showed that baseline TSH level>2.897 mIU·L^(-1)(specificity 91.53%,sensitivity 50.00%)could better predict hypothyroidism(P<0.05).In the general population and lung cancer population,after immune checkpoint inhibitor therapy,the patients with thyroid dysfunction had longer PFS than those with normal thyroid function(HR=0.542,95%CI=0.292-1.007,P<0.05 and HR=0.192,95%CI=0.045-0.813,P<0.05),which were statistically significant.Conclusion After the use of immune checkpo

关 键 词：免疫检查点抑制药 免疫治疗 免疫相关不良事件 甲状腺功能障碍 

分 类 号：R97[医药卫生—药品]