易普利姆玛
垂体炎
医学
黑色素瘤
不利影响
危险系数
内科学
队列
肿瘤科
癌症
免疫疗法
激素
垂体
置信区间
癌症研究
作者
Alexander T. Faje,Donald P. Lawrence,Keith T. Flaherty,Christine Freedman,Riley Fadden,Krista M. Rubin,Justine V. Cohen,Ryan J. Sullivan
出处
期刊:Cancer
[Wiley]
日期:2018-07-05
卷期号:124 (18): 3706-3714
被引量:320
摘要
BACKGROUND It remains unclear whether high doses of glucocorticoids have a negative impact on the efficacy of checkpoint inhibitors. To control for the potential association between immune‐related adverse events (irAEs) and improved survival, this study examined a unique cohort of patients who had the same irAE treated with varying glucocorticoid doses. METHODS In total, 98 patients with melanoma who had ipilimumab‐induced hypophysitis were identified retrospectively in the Partners Healthcare system using an automated electronic medical record query tool. Patients with melanoma who received ipilimumab at Massachusetts General Hospital without developing hypophysitis were listed in an actively maintained institutional patient database. Glucocorticoid doses for patients with hypophysitis were categorized as low dose (LD) or high dose (HD). Survival analyses were performed for patients who received ipilimumab monotherapy. RESULTS Both overall survival (OS) and the time to treatment failure were significantly longer in the LD group compared with the HD group (hazard ratio, 0.24; P = .002 and 0.28, P = .001, respectively). Median OS and the time to treatment failure were not reached in the LD group and were 23.3 and 14.5 months, respectively, in the HD group. All patients who had hypophysitis had improved OS compared with patients who did not have hypophysitis (median, 28.2 vs 9.5 months; P = .0003). This advantage was maintained in the HD group versus the nonhypophysitis group ( P = .02). Radiologic and endocrinologic outcomes and symptom resolution did not differ in the LD group versus the HD group. CONCLUSIONS Among patients with melanoma who had ipilimumab‐induced hypophysitis, those who received higher doses of glucocorticoids had reduced survival. This is the first study to demonstrate a potential negative effect of high glucocorticoid doses on the efficacy of checkpoint inhibitors after an irAE. These findings have potential implications for the management of other irAEs.
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