Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: a systematic review

Objective To summarize the clinical characteristics and immunological and genetic features of patients who developed autoimmune polyendocrine syndrome type II (APS-2) after treatment with immune checkpoint inhibitors (ICIs). Design and methods Several databases (MEDLINE/EMBASE/Cochrane) were searched for studies published between January 2000 and February 2020 involving patients with two or more endocrine disorders after ICI therapy. Results Our final review included 22 articles comprising 23 patients (median age 56 years; 65.2% male patients). Of these patients, 60.9% received anti-programmed cell death 1 (PD-1) therapy, 17.4% received anti-programmed cell death ligand 1 (PD-L1) therapy, and 4.3% received anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monotherapy. Patients underwent a median of four treatment cycles before the onset of the primary adverse event; the median time of onset was 8.5 weeks. Endocrine organs affected by ICI administration included the thyroid gland (18/23, 78.3%), pancreatic islets (17/23, 73.9%), pituitary gland (11/23, 47.8%), and adrenal gland (2/23, 8.7%). Related autoantibodies were detected in 65.2% of patients. In patients with diabetes, glutamic acid decarboxylase antibody was closely related to the development of diabetes ketoacidosis. The human leukocyte antigen genotype was reported in 34.8% (8/23) of patients, 5 (62.5%) of which had risk genotypes. Conclusions As a serious adverse event of ICI treatment, APS-2 is presented with abrupt initiation time and rapid development. Physicians should be aware of potential endocrine disorders and continue monitoring hormone status when treating cancer patients with ICIs.

Automated summary

This study reviewed 22 articles on patients who developed APS-2 after ICI treatment, including a total of 23 patients, the majority of whom were male patients receiving PD-1 therapy. These patients typically developed symptoms of endocrine organ involvement after 8.5 weeks, with 65.2% testing positive for related autoantibodies, where glutamic acid decarboxylase antibody played a key role in the onset of diabetes in some patients.