Retrospective Analysis of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy in Melanoma Patients Reveals Increased Risk Associated With the Hla-B*51:01 Allele

Authors

Mckenzie DiLeo
Samantha Oglesby
Cheuk Hong Leung
Kristen E Pauken
Sahira Farooq
Lauren E Haydu
Shelby L Kubicki
Rebeca Martinez
Macartney Welborn
Sana Zahiruddin
Jun Zou
Kai Cao
Anisha B Patel

Language

English

Publication Date

2-1-2026

Journal

Cancer

DOI

10.1002/cncr.70262

PMID

41563778

PMCID

PMC12822812

PubMedCentral® Posted Date

1-21-2026

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Melanoma, Retrospective Studies, Immune Checkpoint Inhibitors, Female, Male, Middle Aged, Alleles, Aged, Skin Neoplasms, Adult, HLA-B Antigens, Risk Factors, Aged, 80 and over, Genetic Predisposition to Disease, biomarkers, drug eruptions, human leukocyte antigens (HLA), HLA‐B*51:01 antigen, immune checkpoint inhibitors (ICI), immunotherapy, major histocompatibility complex (MHC), melanoma

Published Open-Access

yes

Recommended Citation

DiLeo, Mckenzie; Oglesby, Samantha; Leung, Cheuk Hong; et al., "Retrospective Analysis of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy in Melanoma Patients Reveals Increased Risk Associated With the Hla-B*51:01 Allele" (2026). Faculty, Staff and Student Publications. 6399.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6399