Endocrine Autoantibodies Determine Immune Checkpoint Inhibitor-induced Endocrinopathy: A Prospective Study

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2022 Mar 18

PMID 35303106

Authors

Artak Labadzhyan

Kristopher Wentzel

Omid Hamid

Kamlynn Chow

Sungjin Kim

Lawrence Piro

Shlomo Melmed

Affiliations

Soon will be listed here.

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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