Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: a systematic review
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ORIGINAL ARTICLE
Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: a systematic review Zhe Zhao1 · Xinfeng Wang2 · Xiu‑qi Bao1 · Jingwen Ning1 · Meiyu Shang1 · Dan Zhang1 Received: 25 May 2020 / Accepted: 14 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords Autoimmune polyendocrine syndrome · Immune checkpoint inhibitors · Endocrinopathy · Immune-related adverse effect Abbreviations ACA Adrenal cortex antibody APS-2 Autoimmune polyendocrine syndrome type II CTLA-4 Cytotoxic T-lymphocyte antigen 4
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02699-1) contains supplementary material, which is available to authorized users. * Dan Zhang [email protected] 1
State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China
Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
2
DKA Diabetes ketoacidosis; FSH, follicle-stimulating hormone FT4 Free thyroxine GAD Glutamic Acid Decarboxylase HLA Human leukocyte antigen ICI Immune checkpoint inhibitor irAE Immun
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