Prospective Study of ICI-Induced Endocrinopathies

Artak Labadzhyan, Kristopher Wentzel, Omid Hamid, Kamlynn Chow, Sungjin Kim, Lawrence Piro, Shlomo Melmed
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 7, July 2022, Pages 1976–1982
https://doi.org/10.1210/clinem/dgac161

Abstract

Context

Incidence and awareness of endocrine-related adverse events (ERAE) associated with use of immune checkpoint inhibitors (ICI) has grown with increased ICI use, yet mechanisms for ERAE prediction, surveillance, and development are not well established.

Objective

We prospectively evaluated the impact of endocrine autoimmunity on ERAE development and overall survival (OS).

Methods

Adults ≥ 18 years of age prescribed ICI treatment for advanced or metastatic solid tumors and no known active/past endocrine disorders were eligible for enrollment. Thyroid, adrenal, and pancreatic antibodies as well as hormone levels were assessed prior to ICI treatment and at 8 to 9 weeks and 36 weeks after treatment for ERAE in relation to presence and changes in endocrine-specific antibodies, hormone levels, and OS.

Results

Sixty patients were enrolled and ERAE were detected in 14 (23.3%), with a median onset of 52 days (IQR, 38.5–71.5) after first ICI dose. Hypothyroidism occurred in 12 (20%) patients, and 2 (3.33%) patients developed hypophysitis. Diabetes and primary adrenal insufficiency were not observed. Antibodies were detected in 14 patients (11 at baseline, 3 developed during follow-up) and their presence was significantly associated with ERAE (R² 59.3%, P < 0.001). Thyroid peroxidase antibody (20%) and thyroid-stimulating immunoglobulin (3.3%) were most common, and anti-GAD was present in 1 patient. The presence of ERAE was associated with a more favorable OS (P = 0.001).

Conclusion

Endocrine-specific autoantibodies play an important role in ERAE pathogenesis and may serve as predictive markers for early identification and treatment of ICI-induced endocrinopathies.

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