Kaur Aneet, Doberstein Taylor, Amberker Rachana Ramesh, Garje Rohan, Field Elizabeth Hirak, Singh Namrata
Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA.
ThedaCare Orthopedic Care-Rheumatology, Neenah, Wisconsin.
Medicine (Baltimore). 2019 Oct;98(41):e17348. doi: 10.1097/MD.0000000000017348.
Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.
免疫检查点抑制剂(ICI),如细胞毒性T淋巴细胞相关蛋白4(抗CTLA4)和程序性死亡细胞蛋白1(抗PD1),彻底改变了癌症治疗方式。随着ICI的广泛应用,越来越多的免疫相关不良事件(irAE)被报道。我们的目的是调查新出现的irAE的频率和性质,并报告ICI治疗后既往自身免疫性疾病复发的频率。
我们对2014年1月至2016年4月在我们三级医疗中心接受抗PD1或抗CTLA4或联合治疗的所有癌症患者进行了回顾性病历审查。提取了人口统计学数据、癌症类型和分期、irAE(ICI治疗期间新出现的免疫紊乱和既往自身免疫性疾病的疾病复发)以及药物治疗信息。
在研究期间,我们确定了220例接受ICI治疗的患者,其中27%(60/220)发生了irAE。抗CTLA4组中11%的患者和抗PD1治疗患者中16%的患者发生了irAE。在发生irAE的患者中,28%因irAE而停止了癌症治疗。21.4%的患者自身免疫性疾病复发,但只有1例需要停止免疫治疗。
irAE是临床专家需要了解的一个重要的新出现的疾病实体。我们的研究表明,在密切监测下,ICI可安全用于既往有自身免疫性疾病的患者。然而,对于如何系统评估和管理irAE患者以及识别irAE的预测因素,仍有很大的未满足需求。