Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study.

ABSTRACT

PURPOSE: Immune checkpoint inhibitor (ICI) induced type 1 diabetes (T1D) and pituitary dysfunction are life-threatening adverse events, yet there is little clinical data available. We aimed to investigate the clinical characteristics of patients with these adverse events and report their human leukocyte antigen (HLA) profile to determine its relevance. METHODS: This is a single-center prospective study. We enrolled patients with cancers who were administered ICI and diagnosed as ICI induced T1D (ICI-T1D) and pituitary dysfunction (ICI-PD). Clinical data and extracted DNA from blood samples were collected. HLA typing was performed using next-generation sequencing. We compared our results with those previously reported in healthy controls and investigated the correlation between HLA and the occurrence of ICI-T1D and ICI-PD. RESULTS: We identified 914 patients treated with ICI in our facility from 1st September, 2017 to 30th June, 2022. Six of these patients developed T1D and 15 developed pituitary dysfunction. The duration from the initiation of ICI treatment to the onset of T1D or pituitary dysfunction averaged 492 ± 196 days and 191 ± 169 days. Among the six patients with T1D, two were positive for anti-GAD antibody. The frequencies of HLA-DR11, -Cw10, -B61, -DRB1*1101, and -C*0304 were significantly higher in patients with ICI-T1D than in controls. The frequencies of HLA-DR15 and -DRB*1502 were significantly higher in patients with ICI-PD than in controls. CONCLUSION: This study revealed the clinical characteristics of ICI-T1D and ICI-PD and the association between specific HLAs and these adverse events.