{"title":"Endocrine adverse events of immune checkpoint inhibitors: results of a single-center study","authors":"E. Poddubskaya, M. Sekacheva, A. Guryanova","doi":"10.47093/22187332.2019.4.4-11","DOIUrl":null,"url":null,"abstract":"Immune checkpoint inhibitors (ICPIs) agents can cause endocrine immune-related adverse events (irAEs).Aim. Determine the incidence, time of onset and risk factors of endocrine irAEs in cancer patients treated with anti-PD1 and anti-CTLA-4 immunotherapy.Materials and methods. This is a retrospective single-center study that included 61 patients aged 28 to 81 years with diagnosed cancer of the lungs, ovaries, esophagus, stomach, bladder, kidney, and pleural mesothelioma. 44 (72%) patients received anti-PDL1/anti-PD1 monotherapy and 17 (28%) received a combination of anti-PD1 + anti-CTLA-4. Calculated: odds ratio (OR) and 95% confidence interval (CI).Results. The incidence of endocrine irAEs was 23% (14 patients): thyroiditis (13%), hypophysitis (8%), adrenal insufficiency and diabetes mellitus (2–3%). IrAEs occurred in 9 (20%) patients with monotherapy and in 5 (35%) patients when using a combination of drugs (p=0.318). The average time of onset of irAEs did not differ depending on the applied regimen and amounted to 6 [4–18] weeks. Symptomatic irAEs developed in 2 (13%) patients. Discontinuation of ICPI therapy due to irAE was not required in any case. Risk factors: age younger than 61 years old – OR 4.4 (95% CI 1.198–16.242), female OR 2.4 (95% CI 0.67–8.591), presence of stage IV disease – OR 2.4 (95% CI 0.689–8.362), combination therapy OR 1.855 (95% CI 0.548–6.277), previous endocrine pathology – OR 0.813 (95% CI 0.152–4.356).Conclusions. The incidence of endocrine irAEs when using ICPI is 23%. Thyroiditis and hypophysitis develop more often. The odds are higher in patients younger than 61 years. In most cases, irAEs are not symptomatic and do not require discontinuation of ICPI therapy.","PeriodicalId":129151,"journal":{"name":"Sechenov Medical Journal","volume":"57 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2019-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sechenov Medical Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.47093/22187332.2019.4.4-11","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
Abstract
Immune checkpoint inhibitors (ICPIs) agents can cause endocrine immune-related adverse events (irAEs).Aim. Determine the incidence, time of onset and risk factors of endocrine irAEs in cancer patients treated with anti-PD1 and anti-CTLA-4 immunotherapy.Materials and methods. This is a retrospective single-center study that included 61 patients aged 28 to 81 years with diagnosed cancer of the lungs, ovaries, esophagus, stomach, bladder, kidney, and pleural mesothelioma. 44 (72%) patients received anti-PDL1/anti-PD1 monotherapy and 17 (28%) received a combination of anti-PD1 + anti-CTLA-4. Calculated: odds ratio (OR) and 95% confidence interval (CI).Results. The incidence of endocrine irAEs was 23% (14 patients): thyroiditis (13%), hypophysitis (8%), adrenal insufficiency and diabetes mellitus (2–3%). IrAEs occurred in 9 (20%) patients with monotherapy and in 5 (35%) patients when using a combination of drugs (p=0.318). The average time of onset of irAEs did not differ depending on the applied regimen and amounted to 6 [4–18] weeks. Symptomatic irAEs developed in 2 (13%) patients. Discontinuation of ICPI therapy due to irAE was not required in any case. Risk factors: age younger than 61 years old – OR 4.4 (95% CI 1.198–16.242), female OR 2.4 (95% CI 0.67–8.591), presence of stage IV disease – OR 2.4 (95% CI 0.689–8.362), combination therapy OR 1.855 (95% CI 0.548–6.277), previous endocrine pathology – OR 0.813 (95% CI 0.152–4.356).Conclusions. The incidence of endocrine irAEs when using ICPI is 23%. Thyroiditis and hypophysitis develop more often. The odds are higher in patients younger than 61 years. In most cases, irAEs are not symptomatic and do not require discontinuation of ICPI therapy.
免疫检查点抑制剂(icpi)可引起内分泌免疫相关不良事件(irAEs)。测定抗pd1和抗ctla -4免疫治疗的肿瘤患者内分泌irae的发生率、发病时间及危险因素。材料和方法。这是一项回顾性的单中心研究,纳入了61例年龄在28至81岁之间,诊断为肺癌、卵巢癌、食道癌、胃癌、膀胱癌、肾癌和胸膜间皮瘤的患者。44例(72%)患者接受抗pdl1 /抗pd1单药治疗,17例(28%)患者接受抗pd1 +抗ctla -4联合治疗。计算方法:比值比(OR)和95%可信区间(CI)。内分泌类irAEs发生率为23%(14例):甲状腺炎(13%)、垂体炎(8%)、肾上腺功能不全和糖尿病(2-3%)。单药组有9例(20%)患者发生irae,联合用药组有5例(35%)患者发生irae (p=0.318)。irae的平均发病时间不因应用方案而异,均为6周[4-18]。2例(13%)患者出现症状性irae。在任何情况下都不需要因irAE而停止ICPI治疗。危险因素:年龄小于61岁- OR 4.4 (95% CI 1.188 - 16.242),女性OR 2.4 (95% CI 0.67-8.591),存在IV期疾病- OR 2.4 (95% CI 0.689-8.362),联合治疗OR 1.855 (95% CI 0.548-6.277),既往内分泌病理- OR 0.813 (95% CI 0.154 - 4.356)。使用ICPI时,内分泌irae的发生率为23%。甲状腺炎和垂体炎更常发生。年龄小于61岁的患者患病几率更高。在大多数情况下,irae没有症状,不需要停止ICPI治疗。