Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICIs) including programmed-death cell-1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) re-activate T lymphocytes and promote cancer cell death. Immune-related adverse events (irAEs) are common in cancer patients receiving ICIs. Endocrine irAEs include primary thyroid dysfunction, hypophysitis, type 1 diabetes mellitus (T1DM) and primary adrenal insufficiency. These endocrinopathies may require a treatment break until toxicity resolves.

Methods: A retrospective analysis was performed at our centre in all cancer patients receiving PD1, PDL1 and CTLA4 inhibitors. Data collection included treatment details, characteristics of acute endocrine manifestations, history of autoimmune disease and overall survival, defined as the time between treatment initiation to death or 1st March 2022 when data collection ceased.

Results: 400 cancer patients (249 male, 62.2%; 151 female, 37.8%) were identified. 15% (n=60) of these developed an endocrine irAE: 64.1% primary thyroid dysfunction (n=41), 15.6% primary adrenal insufficiency (n=10), 12.5% hypophysitis (n=8). 7.8% type 1 diabetes mellitus (n=5). All cases of new onset diabetes mellitus presented acutely with diabetic ketoacidosis, were not associated with adjuvant glucocorticoid use and developed late in treatment. By multiple logistic regression, men were less likely to develop an irAE (OR=2.73, 95% CI [1.7, 5.8]) (P<0.001). A history of autoimmune disease or non-endocrine irAEs were not associated with developing an endocrine irAE. Overall survival was higher in patients developing combined endocrine and non-endocrine irAEs (P<0.001) and in patients developing an endocrine irAE(P<0.01).

Conclusion: Endocrine complications from immunotherapy may present acutely and late in treatment. Women receiving ICIs are at higher risk of ICI-induced endocrinopathies. Interestingly, this study shows that development of endocrine irAEs alone or in combination with non-endocrine irAEs are associated with a favourable overall cancer survival. Future prospective studies are needed to further elucidate the links between endocrine manifestations of ICI treatment and cancer survival.