High‐dose glucocorticoids for the treatment of ipilimumab‐induced hypophysitis is associated with reduced survival in patients with melanoma
Top Cited Papers
- 5 July 2018
- Vol. 124 (18), 3706-3714
- https://doi.org/10.1002/cncr.31629
Abstract
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. Cancer 2018. © 2018 American Cancer Society.Keywords
This publication has 29 references indexed in Scilit:
- Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor RegimensJAMA Oncology, 2018
- Resistance to checkpoint blockade therapy through inactivation of antigen presentationNature Communications, 2017
- Hypophysitis: Evaluation and ManagementClinical Diabetes and Endocrinology, 2016
- Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insightsPituitary, 2015
- Hypophysitis: a single-center case seriesPituitary, 2014
- Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients With Metastatic MelanomaJournal of Clinical Endocrinology & Metabolism, 2014
- Primary hypophysitis: a single-center experience in 16 casesJournal of Neurosurgery, 2004
- Lymphocytic and granulocytic hypophysitis: a single centre experience.British Journal of Neurosurgery, 2001
- Lymphocytic and Granulomatous Hypophysitis: Experience with Nine CasesNeurosurgery, 1997
- Hypophysitis in surgical and autoptical specimensActa Neuropathologica, 1995