Cancer. 2026 Feb 1;132(3):e70262. doi: 10.1002/cncr.70262.
ABSTRACT
BACKGROUND: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.
METHODS: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as monotherapy or in combination, and had HLA typing available. This analysis spans from 2003 to 2023 with a focus on cutaneous irAEs. Statistical analyses were conducted to assess the association between HLA alleles and irAEs.
RESULTS: Our analysis revealed that the HLA-B*51:01 allele was associated with a higher risk of cutaneous irAEs after adjusting for ICI regimen (hazard ratio: 1.71 [95% CI, 1.12-2.61], p = .013.) CONCLUSION: This is the largest study to link an HLA allele with ICI-induced cutaneous irAEs. The findings may support the use of HLA typing as an initial screen for developing irAEs, providing a simple, straightforward metric that can be rapidly performed on patients prior to initiation of ICIs. However, further research is needed across different cancer and toxicity types.
PMID:41563778 | DOI:10.1002/cncr.70262
