Introduction: Whilst effective, targeted checkpoint inhibitor monoclonal antibodies are associated with immune-related adverse events including endocrinopathies. Increased licensed oncological indications for these agents raise the need for effective screening, monitoring and ongoing treatment of endocrinopathies. The aim of our study was to investigate potential predictive factors that may identify patients at risk of endocrinopathies.
Method: Retrospective audit of 160 patients receiving treatment in a single center with Ipilimumab, Pembrolizumab and Nivolumab individually or in combination.
Results: Thyroid dysfunction in 9.3% (15/160) and hypophysitis in 7.5% (12/160) were the commonest endocrine effects. There was no significant difference in the mean age of affected (59 y, 3382) and unaffected (66 y, 3083) patients nor in gender susceptibility (Men 82/129 unaffected to 17/31 affected, Women 49/129 unaffected to 14/31 affected, P=0.99).
Early symptoms of thyroid dysfunction (hyperthyroidism) and hypophysitis (headache or visual disturbance) were absent in the majority. There was no consistent change in prolactin or gonadotrophin level. MRI pituitary showed no characteristic changes. Posterior pituitary function remained unaffected. Thyroid antibodies were tested in eight out of fifteen with thyroid dysfunction and four were positive. Recrudescence of quiescent Graves ophthalmopathy occurred in one patient and insulin deficiency characterised by ketoacidosis occurred in two patients with pre-existing type 2 diabetes mellitus. The time to development of endocrinopathy was 324 weeks with no obvious safe cut-off for exclusion. Pembrolizumab was predominantly associated with thyroid dysfunction (53%), whereas hypophysitis (41%) was more frequent with Ipilimumab.
Conclusion: Age, sex, and early symptomatology were not helpful markers in predicting risk for endocrinopathy. Although more frequent early in treatment, endocrine dysfunction could occur almost 6 months after initiating treatment. Type 2 diabetes and Graves disease in remission significantly increases risk. Vigilant long-term monitoring is warranted in this cohort particularly in those with previous autoimmune conditions.