Artak Labadzhyan1, Kristopher Wentzel2, Omid Hamid2, Kamlynn Chow2, Sungjin Kim3, Lawrence Piro2, Shlomo Melmed1. 1. Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 2. The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, CA, USA. 3. Biostatistics and Bioinformatics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
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.
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.
Authors: Jacqueline Jonklaas; Antonio C Bianco; Andrew J Bauer; Kenneth D Burman; Anne R Cappola; Francesco S Celi; David S Cooper; Brian W Kim; Robin P Peeters; M Sara Rosenthal; Anna M Sawka Journal: Thyroid Date: 2014-12 Impact factor: 6.568
Authors: A M Menzies; D B Johnson; S Ramanujam; V G Atkinson; A N M Wong; J J Park; J L McQuade; A N Shoushtari; K K Tsai; Z Eroglu; O Klein; J C Hassel; J A Sosman; A Guminski; R J Sullivan; A Ribas; M S Carlino; M A Davies; S K Sandhu; G V Long Journal: Ann Oncol Date: 2017-02-01 Impact factor: 32.976
Authors: Alexander T Faje; Ryan Sullivan; Donald Lawrence; Nicholas A Tritos; Riley Fadden; Anne Klibanski; Lisa Nachtigall Journal: J Clin Endocrinol Metab Date: 2014-07-31 Impact factor: 5.958