Genetic drivers of severe skin toxicity with immune checkpoint inhibitors (ICIs) in Asian patients.

• DOI: 10.1200/jco.2024.42.16_suppl.2667
• Publication Date: 2024-06-04T19:28:39Z
• Authors: Kohei Yoshimine; Hiroki Goto; Kana Yamada; Tamaki Fukuyama; Tetsuro Oda; Runa Iwakami; Koji Takahashi; Monika Dulloo Kaul; G Scott Chandler; Rajat Mohindra; Katrin Madjar
• Keywords: Immune checkpoint

2667 Background: ICIs may cause severe skin toxicity associated with significant patient (pt) impact. Published data suggests Asian pts might be at higher risk of immune-related adverse events (SirAEs). Variation in human leukocyte antigen (HLA) is known to predispose autoimmune (AI) conditions, but there limited understand genetic drivers SirAEs. Methods: The incidence SirAEs was correlated 30 HLA alleles interest 2 cohorts totaling 18 (Dermatitis bullous n=4, Erythema multiforme n=10, Stevens-Johnson syndrome n=3, Toxic eruption n=1) treated atezolizumab (A) across tumor types as monotherapy or part combinations- 8 Japanese received A a non-interventional study (trial ID: UMIN000048702) and 10 were enrolled Roche trials A. Data from the cases compared 3 different controls identified (i.e. without any irAEs n=148, n=225, n=390). For each allele, positive predictive value (PPV), negative (NPV), sensitivity, specificity, (unadjusted) odds ratio (OR) corresponding 95%-confidence interval (CI) evaluated. Case-control populations obtained by risk-set sampling exact matching on indication, treatment arm sex, used age-adjusted conditional logistic regression models assess associations between allele Results: There an association some SirAEs, sensitivity low (<30%) 1-NPV only slightly smaller than background prevalence. Results for five OR>1.5 either unadjusted adjusted analysis are presented table. consistent three control populations. Conclusions: Five previously reported AI disorders receiving Although effect size insufficient considered clinically relevant, further research warranted better characterize pt-level Asians pts. Clinical trial information: UMIN000048702 . [Table: see text]