High‐dose glucocorticoids for the treatment of ipilimumab‐induced hypophysitis is associated with reduced survival in patients with melanoma

Abstract

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.

Immune‐related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies

“…The management of irAEs is based on clinical experience and requires corticosteroid immunosuppression as first‐line therapy . Although the impact of immunosuppression on the overall survival of patients is unclear, the possibility that steroids may adversely impact on antitumour responses and/or overall survival remains a consideration …”

Immune-Related Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors

“…For grades 3 and 4, irAEs treatment should be permanently discontinued, and high-dose corticosteroid therapy (prednisone at 1–2 mg/kg/day) initiated until irAEs drop to grade 1 or lower. Interestingly, a very recent study showed that treatment of ipilimumab induced hypophysitis with high-dose corticosteroids is associated with increased mortality in melanoma patients suggesting that management of irAEs is nuanced beyond typical immunosuppression [37•]. Currently, it is unclear whether anti-TNF therapy should be administered before the development of adverse events particularly in the adjuvant setting.…”

Emergency management of immune‐related hypophysitis: Collaboration between specialists is essential to achieve optimal outcomes

“…These guidelines also encourage continuation of CPI therapy, an issue not addressed by Faje et al 1 We would appreciate insight into the proportions of patients in the study cohort continuing CPI therapy after developing hypophysitis and the implications for the development of other immune-mediated complications of CPI therapy and survival.The confirmation that patients treated with lower doses of glucocorticoids for CPI-induced hypophysitis have superior survival rates reinforces the importance of ensuring that patients are managed optimally. Furthermore, that survival is better for patients treated with physiological replacement doses of glucocorticoids versus higher doses has clear implications for acute care physicians and nononcologists, who are increasingly likely to be the first point of contact for patients presenting acutely with this potentially fatal complication of CPI therapy.…”

“…These guidelines also encourage continuation of CPI therapy, an issue not addressed by Faje et al 1 We would appreciate insight into the proportions of patients in the study cohort continuing CPI therapy after developing hypophysitis and the implications for the development of other immune-mediated complications of CPI therapy and survival. 2 These guidelines advocate for physiological doses, rather than pharmacological doses, of glucocorticoids for hypophysitis-induced adrenocorticotropic hormone deficiency.…”