Correlation of patient HLA class I genotypes with severe immune-related adverse events: A retrospective study in Chinese population.

10586 Background: Immune checkpoint inhibitors (ICIs) are effective in multiple tumors. However, about 10% of immune-related adverse events (irAEs) are severe and can have serious or even life-threatening consequences for patients. We investigated whether Human leukocyte antigen (HLA) genes predispose to and thus hold a predictive role of developing of severe irAEs in Chinese population. Methods: In a case/control study, we collected data from patients with metastatic cancer treated with ICIs and developed severe irAEs (Grade ≥3 and required hospitalization). Patients treated with ICIs without any irAEs were used as controls. Data was collected from15th Nov, 2019 until 10th Oct, 2023. HLA typing was performed via next generation sequencing. Results: We enrolled 83 patients with severe irAEs and 286 patients treated with ICIs without any irAEs. We found HLA-B*15:27 (OR=9.1, X 2 1,95 = 7.2, P = 0.008) and HLA-C*04:01 (OR=2.5, X 2 1,95 = 7.0, P =0.008) were significantly associated with severe overall irAEs risk. When assessing irAE individually, a significant association between HLA-B*13:02 and serious myocarditis (OR = 3.4, X 2 1,95 = 6.2, P =0.01) as well as striking enrichment for HLA-A*02:03 haplotypes in severe adrenal insufficiency (OR = 10.0, X 2 1,95 = 19.1, P<0.0001) were observed. Conclusions: Specific HLA alleles were associated with severe irAEs. Consideration of pre-prescription HLA typing and vigilance for serious reactions to ICIs are warranted.