Context: Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have nonspecific clinical presentations and variable timelines, making their early diagnosis challenging.
Objective: To identify risk factors, timelines, and prognosis associated with irEEs development.
Design and setting: Retrospective observational study within the Cleveland Clinic center.
Patients: Metastatic cancer adult patients who received ICIs were included.
Methods: 570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival.
Main outcome measures: Incidence of irEEs, time to irEEs development and overall survival of patients who develop irEEs.
Results: The final cohort included 551 patients. The median time for the diagnosis of irEEs was 9 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. Forty-five percent of patients with irEEs had adequate cancer response to ICI compared to 28.3% of patients without irEEs (P = 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs (P < 0.001).
Conclusions: In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.
Keywords: cancer; endocrine toxicities; immune-checkpoint inhibitors; immune-related adverse events.
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.