Occurrence and Treatment of Endocrinologic Adverse Reactions Associated with Immune Checkpoint Inhibitors: a Single-center Real-world Study

Abstract

Background Immunotherapy-related endocrine adverse reactions are relatively common, which often lead to serious outcomes if not treated in time. However, the incidence of immunotherapy-related endocrine adverse reactions varies widely in previous literature reports without standard processing. Objective To investigate the occurrence and treatment process of endocrinologic adverse reactions caused by immune checkpoint inhibitors (ICIs) in the real world. Methods The clinical data of 204 patients with solid tumors treated with ICIs at the Third People's Hospital of Zhengzhou from January 2019 to March 2022 was retrospectively analyzed, the endocrinologic adverse reactions occured their treatment were observed and standardized management was conducted according to the adverse reactions grading. Results A total of 204 patients with solid tumors were included, involving 139 male patients and 65 female patients, with a median age of 65.4 (8.0, 88.4) years. The types of solid tumor were predominantly non-small cell lung cancer (43.1%) , the treatment drugs were mainly sindilizumab (47.1%) , and the treatment patterns were predominantly immunotherapy combined with targeted agents (57.4%) . 12 patients developed ICIs-related endocrinologic adverse reactions, including 9 cases (4.4%) of hypothyroidism (1 case of gradeⅠ, 7 cases of grade Ⅱ, 1 case of grade Ⅲ) with the median onset time of 7 (6, 10) weeks after the treatment of immunological drugs, 1 case (0.5%) of hyperthyroidism (gradeⅠ) occurred 9 weeks after the immunotherapy, 1 case (0.5%) of type 1 diabetes (gradeⅣ) occurred 6 weeks after auto-immunotherapy, 1 case (0.5%) of adrenal dysfunction (gradeⅢ) occurred 7 weeks after immunotherapy. All the 12 patients with endocrinologic adverse reactions were treated in time according to the hierarchical management process, and all their symptoms were improved or returned to normal, and continued to be treated with ICIs. Conclusion The risk of endocrinologic adverse reactions in the endocrine system is relatively high during the use of ICIs, especially abnormal thyroid function, which requires regular detection of endocrine indicators during treatment, timely intervention will not affect the subsequent treatment of ICIs.

Keywords

• immune checkpoint inhibitors|drug-related side effects and adverse reactions|hypothyroidism|hyperthyroidism|diabetes mellitus, type 1|adrenal insufficiency|programmed death receptor 1|programmed death ligand-1|immune-related adverse events