THU092 Characterizing Immune Checkpoint Inhibitor Induced Hypophysitis In A Large Urban Health Care System
Authors: Gogerly-Moragoda Mahalya , Khawaja Umar Sharif , Cheesman Khadeen C , Leiter Amanda , Gallagher Emily J 
Published: October 2023

Abstract
Disclosure: M. Gogerly-Moragoda: None. U. Sharif Khawaja: None. K.C. Cheesman: None. A. Leiter: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals, Flare Therapeutics, Seagen, SynDevRx.
INTRODUCTION Over the past decade, immune checkpoint inhibitors (ICIs) have transformed cancer therapy in multiple tumor types and improved outcomes. Endocrine immune related adverse events are well recognized side effects of ICIs. ICI induced hypophysitis is potentially life-threatening if not identified and treated. The present study examines the incidence and presentation characteristics of hypophysitis in a real-world cohort including a multitude of ICIs and tumor types. METHODS We conducted a retrospective analysis of all patients treated with ICIs at a large health system from 2011-2020. Patient demographics, type of cancer, type of ICI, endocrine symptoms and laboratory values were collected to characterize hypophysitis within the cohort. RESULTS A total of 1703 patients were treated with ICIs from 2011-2020 of whom 32 (1.9%) developed clinically apparent hypophysitis. Of the 32 patients, 26 patients were confirmed to have secondary adrenal insufficiency (AI), with 6 possible secondary AI. A majority were diagnosed in the outpatient setting (n=21, 66%). For those with hypophysitis, the most common tumor type was melanoma (n=12, 38%), followed by lung cancer (n=9, 28%) and genitourinary cancers (n=8, 25%). Combination cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, ipilimumab and programmed cell death protein 1 (PD-1) inhibitor, nivolumab (n=9, 28%) was the most common regimen, followed by monotherapies ipilimumab (n=6, 19%), nivolumab (n=6, 19%), pembrolizumab (n=6, 19%), the programmed cell death ligand 1 (PD-L1) inhibitor atezolizumab (n=3, 9%), with the remainder on durvalumab or combination durvalumab and tremelimumab. The most common presenting symptom was fatigue (n=21, 66%) with headache (n=8, 25%) and vision changes (n=2, 6%) being less common. The median time to presentation was 5 months with most presenting within 12 months of starting ICI (n=24, 75%). However, a subset of patients presented after 18 months on treatment (n=6, 19%), none of whom received ipilimumab. Seven patients underwent cosyntropin stimulation tests and six had muted responses, despite having low or inappropriately normal ACTH levels. DISCUSSION In this real-world dataset, we found a low percentage of hypophysitis across multiple tumor and ICI types. Secondary AI was most commonly seen with ipilimumab treatment. Notably, the subset of patients who presented after 18 months were all on PD-1 / PD-L1 inhibitors, which potentially indicates a distinct mechanism of hypophysitis with these agents compared with CTLA-4 inhibitors, and the new need to monitor these patients with labs and symptom review beyond the initial few months from ICI start. The muted cortisol response to cosyntropin was surprising in the setting of acute hypophysitis and warrants further investigation in these patients.
Presentation: Thursday, June 15, 2023