Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors

• DOI: 10.1136/jitc-2021-002493
• Publication Date: 2021-05-19T13:05:13Z
• Authors: Tomoko Kobayashi; Shintaro Iwama; Daisuke Sugiyama; Yoshinori Yasuda; Takayuki Okuji; Masaaki Ito; Sachiko Ito; Mariko Sugiyama; Takeshi Onoue; Hiroshi Takagi; Daisuke Hagiwara; Yoshihiro Ito; Hidetaka Suga; Ryoichi Banno; Hiroyoshi Nishikawa; Hiroshi Arima
• Keywords: 0301 basic medicine; Time Factors; Genotype; Pituitary Diseases; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Risk Assessment; 3. Good health; 03 medical and health sciences; Gene Frequency; HLA Antigens; Predictive Value of Tests; Risk Factors; Case-Control Studies; Pituitary Gland; Immunotherapy Biomarkers; Humans; Prospective Studies; Immune Checkpoint Inhibitors; RC254-282; Biomarkers; Autoantibodies

Background Pituitary dysfunction is a life-threatening immune-related adverse event (irAE) induced by immune checkpoint inhibitors (ICIs). To date, it not possible to identify patients who may develop pituitary irAEs prior ICI treatment. The aim of this study was characterize the predisposition for ICI-induced analyzing anti-pituitary antibodies (APAs) and human leukocyte antigens (HLAs). Methods In case–control study, APAs HLA alleles were analyzed in 62 (17 developed isolated adrenocorticotropic hormone deficiency (ICI-IAD), 5 hypophysitis (ICI-H) 40 did irAEs) treated with ICIs between November 2, 2015, March 31, 2020, at Nagoya University Hospital. main outcome measures association development baseline after treatment alleles. Results Eleven 17 (64.7%) ICI-IAD had baseline, whereas positive only 1 (2.5%) control patients. Although negative all ICI-H, they become before onset ICI-H 3 4 several weeks ipilimumab administration. At 15 (88.2%) (80%) patients, respectively. prevalence HLA-Cw12, HLA-DR15, HLA-DQ7, HLA-DPw9 significantly higher ICI-IAD, that HLA-Cw12 HLA-DR15 than controls. Conclusions This showed distinct overlapped patterns ICI-H. Our findings also treatment, together susceptible alleles, could predictive biomarkers Trial registration number UMIN000019024.