SUN-487 Incidence and Natural History of Hypophysitis Secondary to Check-Point Inhibitor Therapy at a Tertiary Center

Hypophysitis is a known adverse effect of immune checkpoint inhibitor therapy. These drugs are being increasingly used for treatment of various cancers. Thus, it is crucial to understand the incidence and natural history of hypophysitis to help us improve its management. Aim - To determine the incidence of hypophysitis associated with ipilimumab, nivolumab and pembrolizumab at our center and describe its natural history. Methods – We performed a retrospective study of patients treated with pembrolizumab, nivolumab, ipilimumab or combination of these drugs between Aug 2013 and Jun 2018. Files were reviewed for cancer history and immune related adverse effects. Patients with hypophysitis had their clinical status, biochemistry and treatment documented at 0,1.5, 3, 6, 9 months and at the most recent follow up. Results – Of 115 patients identified, 14 developed hypophysitis. Of these, 8 of 17 patients had received combination ipilimumab and nivolumab, 1 of 6 had received ipilimumab, 4 of 61 had received nivolumab and 1 of 23 had received pembrolizumab. The median time to hypophysitis from initial dose was 98 days. At diagnosis, 78% had thyroid axis involvement, 3/11 had resolved at 6 weeks. Only 50% had a paired ACTH/cortisol requested at diagnosis. 100% had evidence of adrenal insufficiency with no patient recovering their adrenal axis. Gonadal axis was involved in 5/8 at diagnosis and 3/5 had normalized at 6 weeks. All patients received high dose steroids at diagnosis with a large range of time to physiological dosing (4-311 days), median 56. Conclusion –Hypophysitis is a common adverse effect, especially with combination ipilimumab and nivolumab. Most hormone deficiencies present at 6 weeks appear to be permanent. It is important to have early endocrinology involvement to ensure appropriate investigation and management.