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1237 Long term outcomes of severe endocrine immune-related adverse events (irAEs): adrenal insufficiency (AI) and insulin-dependent diabetes (IDDM)
  1. Ben Nguyen1,
  2. Neil J Shah2,
  3. Andrea Knezevic3 and
  4. Monica Girotra3,4
  1. 1SUNY Downstate, Brooklyn, NY, USA
  2. 2Memorial Sloan Kettering Cancer Center, Washington, DC, USA
  3. 3Memorial Sloan Kettering, New York, NY, USA
  4. 4Weill Medical College, New York, NY, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Immune checkpoint inhibitor induced AI and DM are severe endocrine IrAEs and little is known about their long-term morbidity and associated oncology outcomes.

Methods From January 2010 to September 2022, patients that were diagnosed with ICI induced AI and/or IDDM by a board-certified endocrinologist were studied. Out of the 139 patients identified, 101 had secondary AI, 5 had primary AI, and 33 had IDDM. Patients that had high dose steroid use was defined as a daily dose of hydrocortisone 30mg (or equivalent) for more for 2 months. Secondary AI cohort was subclassified as CTLA-4 based (CTLA-4 C) and non CTLA-4 based cohorts (nCTLA-4 C).

Results Among the 101 patients in the secondary AI cohort, 55 (55%) patients received CTLA-4-based ICI, including 35 (64%) patients who received combination PD-1+CTLA-4 ICI. Melanoma (45%) and genitourinary malignancies (25%) were the most common tumor types. The majority of patients had stage IV disease (74%). 52% and 11% developed hypothyroidism and hypogonadism with secondary AI, respectively. 20% (n=20) of patients received initial treatment with high-dose steroids, including 33% (n=18) of the CTLA-4 cohort and 4% (n=2) of the nCTLA-4 cohort. At a median follow-up of 45.5 months, the majority of patients had undetectable ACTH and cortisol levels (table 1). All patients remained on replacement steroids except for two (2%) patients who had recovery in both ACTH and cortisol values (table 1). Among 33 IDDM patients, all patients received PD-(L)-1 based ICIs combinations. GU and melanoma were the most common tumor types. 94% of patients had stage IV disease. Most patients presented with diabetic ketoacidosis [(DKA, 58%)] and required inpatient support with insulin drip (58%). 70% of patients discontinued ICI after IDDM diagnosis, including 39% primarily due to IDDM. Among 45% patients with long-term data (median follow-up 27 months), all patients remained on insulin (table 1).

Conclusions Our study followed patients with ICI induced AI and/or IDDM with a median follow up time of over 45 months. We found that secondary AI due to CTLA-4-based ICIs tends to occur earlier and presents more with symptoms of headache and hyponatremia, while nausea/vomiting is more common with nCTLA-4 based ICI. Almost all patients required long-term replacement steroids, but most of them were rechallenged with ICI after secondary AI. IDDM occurred predominately after PD(L)-1 based ICIs. Most patients presented with DKA and required hospitalization. All patients remained on long-term insulin and only a small subset of patients continued ICI after IDDM.

Abstract 1237 Table 1

shows the long-term outcomes of patients diagnosed with immune checkpoint inhibitor induced adrenal insufficiency and/or insulin dependent diabetes

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