1010 HLA-B allele frequencies in immune checkpoint inhibitor-associated rheumatologic adverse events
Year: 2026
Type: conference-abstract
Abstract: Background Rheumatologic immune-related adverse events (rh-irAEs) occur in up to 10% of patients treated with immune checkpoint inhibitors (ICI). Prior studies show that the spondyloarthritis-associated HLA-B27 allele does not increase risk of rh-irAEs. Other alleles including HLA-B40 and HLA-B47 have also been linked to inflammatory arthritis (IA) but their association with irAEs remains unexplored. We evaluated HLA-B allele frequency among patients diagnosed with rh-irAEs over a 10-year period.Methods We conducted a retrospective, single-center, observational cohort study of patients seen at MD Anderson Cancer Center’s Rheumatology Clinic between February 15, 2015 to August 15, 2025. For patients who underwent HLA-B typing and received ICI, rh-irAE and non-rheumatologic irAE diagnoses were confirmed through manual chart review. We collected demographic, oncologic, ICI exposure, HLA-B, serologic, and irAE data. Analyses were performed in R (v4.6.0). HLA-B allele frequency was defined as the number of a unique allele and divided by the total number of alleles in the cohort. Exploratory associations between HLA-B alleles and irAEs were assessed using Fisher’s exact test with odds ratios and 95% confidence intervals.Results A total of 132 patients were included ( table 1). Median age was 62 years (IQR 53-69.2), with slight female predominance (54.5%). The cohort was predominantly White (87.9%) and non-Hispanic (84.8%). Melanoma was the most common cancer type (41.8%), followed by breast (12.7%), genitourinary (11.2%), and lung (9.7%). The majority of patients received PD-1 inhibitor monotherapy (56.1%), with median ICI duration of 178 days (IQR 55.2-345.2). 21% of patients had ANA positivity, while RF and CCP positivity were rare (table 1).The most common HLA-B alleles were HLA-B35 (22%), HLA-B44 (21.2%), and HLA-B40 (20.4%). HLA-B27 allele frequency was comparatively low (6.8%). IA was the most common rh-irAE, while other rh-irAEs were relatively rare (table 1). Among non-rheumatologic irAEs, colitis (24.5%), hepatitis (16%), and thyroiditis (12.3%) were most common (table 1). On exploratory analysis, no significant associations were identified between specific HLA-B alleles and any irAEs (table 2). Associations between HLA-B40 and ICI-colitis (OR 3.77 [1.44, 9.68]), HLA-B44 and ICI-adrenalitis (OR 3.74 [0.80, 14.27]), and HLA-B44 and ICI-PMR (OR 2.63 [0.58, 9.31]) trended toward significance (Benjamini-Hochberg adjusted p-values non-significant).Conclusions Patients treated with ICI who developed rh-irAEs exhibited heterogeneous HLA-B allele distribution, with predominance of HLA-B35, HLA-B40, and HLA-B44. These findings underscore the need for larger, well-powered studies with matched comparator cohorts to better characterize associations between specific HLA-B alleles, susceptibility to rh-irAEs and non-rheumatologic irAEs, and overall clinical outcomes.Abstract 1010 Table 1Cohort demographics, serologic data, and irAE frequencyAbstract 1010 Table 2Frequency of irAEs by HLA-B allele
Authors: Lily Xu, Yinghong Wang, Yuanteng Jeff Li
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225170185