期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 7, 页码 1976-1982出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgac161
关键词
immune checkpoint inhibitors; endocrine-related adverse events; autoantibodies
资金
- CTSI Clinical Scholars Grant under the NIH National Center for Advancing Translational Science (NCATS) University of California Los Angeles Clinical Translational Science Institute (UCLA CTSI) [UL1TR001881]
- National Institutes of Health (NIH) [T32DK007770]
This study prospectively evaluated the impact of endocrine autoimmunity on the development of immune checkpoint inhibitor (ICI)-induced adverse events (ERAE) and overall survival (OS). ERAE occurred in 14 patients, with hypothyroidism being the most common. The presence of antibodies was significantly associated with ERAE. The presence of ERAE was associated with a more favorable OS.
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 (R-2 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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