PDF(Pubmed)
Abstract：
Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher\'s exact tests, Student t-tests, Kaplan-Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM.
摘要：
免疫检查点抑制剂（CPI）诱导的糖尿病（CPI-DM）是一种罕见的免疫相关不良事件（irAE）。患者和提供者担心持续的CPIs会使患者面临其他irAE的风险，因此可能会停止治疗。目前,几乎没有数据可以告知这一决定。因此,本研究旨在阐明CPI-DM诊断后停止CPIs是否会影响未来irAE的发展以及进展和死亡等癌症结局.对2015年7月1日至2023年7月5日在UCSF治疗期间发生CPI-DM的患者进行癌症结果和irAE发展分析。费希尔的精确检验，学生t检验,Kaplan-Meier方法,适当时使用Cox回归。在43例CPI-DM患者中，20(47%)在IRAE发生后90天内恢复了CPIs，4例（9%）患者在90天后重新开始，和19（44％）患者从未重新启动。在恢复CPIs的24人中有9人（38％）和停止CPIs的19人中有3人（16％）被诊断出随后的irAE（p=0.17）。两组之间的死亡（p=0.74）或癌症进展（p=0.55）没有显着差异。虽然我们的单机构研究在停止CPIs后没有显示更坏的癌症结果，许多变量会影响结果，我们的研究没有足够的能力来评估。需要一种细致入微的方法来决定在CPI-DM等严重的irAE之后是否继续CPI治疗。
