The burden and clinical trajectory of immune checkpoint inhibitor-induced endocrinopathies: an 8-year experience

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancer patients, but the emergence of ICI-related endocrinopathies (IREs) has introduced new clinical challenges. Despite worldwide recognition of these adverse effects, data from the Middle East is scarce.

Methods: This retrospective-observational study included adult cancer patients who received at least one dose of ICI between January 2015 and January 2023. Descriptive statistics and multivariable regression (MVR) models were applied to delineate the incidence and clinical impact of IREs.

Results: The median age of 649 included patients was 55 years, with male preponderance (70.7%). The incidence of IREs was 26.7%, dominated by primary hypothyroidism (62.4%), insulin deficiency (15%), and primary hyperthyroidism (13.9%). Pembrolizumab (62%) was the most utilized ICI among the study cohort, followed by nivolumab (23.7%), atezolizumab (12.5%), durvalumab (0.9%), avelumab (0.6%) and ipilimumab (0.1%). The mortality rates in the cohort and the IRE subgroup were 43.4% and 42.2%. MVR revealed age (OR 1.02, 95% CI (1.003-1.03), P = 0.02), pre-ICI white-cell (WBC) count (OR 0.94, 95% CI (0.89-0.99), P = 0.04), pembrolizumab (OR 2.6, 95% CI (1.05-6.3), P = 0.04), and nivolumab use (OR 2.6, 95% CI (1.04-6.6), P = 0.04) as significant predictors of IREs. After MVR, factors influencing mortality in the subgroup with IREs included a higher age (OR 1.1, 95% CI 1.04-1.2, P = 0.001) and platelet-to-lymphocyte ratio (OR 1.004, 95% CI 0.7-1.4, P = 0.006).

Conclusions: This first extensive Middle Eastern and South Asian cohort reported a higher-than-previously known incidence of IREs. Hypothyroidism, insulin deficiency, and hyperthyroidism were the commonest IREs, with pembrolizumab being the commonest ICI. IRE development was associated with higher age, a low WBC count, pembrolizumab, and nivolumab use. The development of IREs did not seem to influence mortality. Further research on IREs is imperative to optimize management guidelines in the era of precision medicine.