High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma
High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma
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DOI：
10.1002/cncr.31629
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发表时间：
2018-09-15
期刊：
影响因子：
6.2
通讯作者：
Sullivan, Ryan J.
中科院分区：
文献类型：
--
作者：
Faje, Alexander T.;Lawrence, Donald;Sullivan, Ryan J.
背景：目前尚不清楚高剂量的糖皮质激素是否对检查点抑制剂的疗效产生负面影响。为了控制免疫相关不良事件 (irAE) 与提高生存率之间的潜在关联，本研究检查了一组独特的患者，这些患者患有相同的 irAE，但接受不同剂量的糖皮质激素治疗。方法：使用自动电子病历查询工具，在 Partners Healthcare 系统中回顾性地识别出总共 98 名患有伊匹单抗引起的垂体炎的黑色素瘤患者。在马萨诸塞州总医院接受伊匹单抗治疗但未出现垂体炎的黑色素瘤患者被列入积极维护的机构患者数据库中。垂体炎患者的糖皮质激素剂量分为低剂量（LD）或高剂量（HD）。对接受伊匹单抗单药治疗的患者进行生存分析。结果：与 HD 组相比，LD 组的总生存期 (OS) 和治疗失败时间均显着更长（风险比，0.24；P = 0.002 和 0.28，P = 0.001）。 LD 组的中位 OS 和治疗失败时间尚未达到，HD 组分别为 23.3 个月和 14.5 个月。与没有垂体炎的患者相比，所有患有垂体炎的患者的 OS 均有所改善（中位时间为 28.2 个月 vs 9.5 个月；P = .0003）。与非垂体炎组相比，HD 组保持了这一优势 (P = .02)。 LD 组与 HD 组的放射学和内分泌结果以及症状缓解没有差异。结论：在患有易普利姆玛诱发的垂体炎的黑色素瘤患者中，接受较高剂量糖皮质激素的患者生存率降低。这是第一项证明高剂量糖皮质激素对 irAE 后检查点抑制剂疗效可能产生负面影响的研究。这些发现对其他 irAE 的管理具有潜在影响。 (C) 2018 年美国癌症协会。
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. (C) 2018 American Cancer Society.