Association of IL7 rs16906115 Polymorphism with Adverse Events in Patients with Advanced Lung Cancer Undergoing Immunotherapy

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small cell lung cancer (aNSCLC). However, immune-related adverse events (irAEs) remain a clinical challenge in this context. Genetic variants acting as cis-eQTLs may predict toxicity risk, thereby enabling personalized treatment. We investigated the association between the IL7 rs16906115 polymorphism, adverse events (AEs), and survival outcomes in patients with aNSCLC receiving ICIs. Methods: This retrospective cohort study analyzed 153 patients with aNSCLC treated with ICIs (2018–2023) at two centers in Spain. The final analytical cohort included 124 patients with complete clinical follow-up. IL7 rs16906115 genotyping was performed using TaqMan assays. Associations between genotypes/alleles, AEs, and survival (PFS/OS) were evaluated using logistic regression and Kaplan-Meier analysis. A clinical-genetic predictive model was developed. Results: The minor A allele frequency was 8.5%. Carriers of the A allele (AG/AA genotypes) had significantly higher adverse event rates compared to GG homozygotes (OR = 3.77, 95% CI: 1.16–12.6, p = 0.0081). The as-sociation remained significant after multivariable adjustment (OR = 4.64, 95% CI: 1.50–17.2, p = 0.0203). Crucially, A-allele carriers exhibited significantly shorter Pro-gression-Free Survival compared to non-carriers (median 6.6 vs. 10 months, p = 0.0029). The combined clinical-genetic model achieved superior predictive perfor-mance for toxicity (AUC = 0.67) compared to clinical-only models (AUC = 0.57), suc-cessfully stratifying patients into moderate- and high-risk groups, respectively. Conclusions: IL7 rs16906115 polymorphism represents a potential pharmacogenetic bi-omarker for predicting adverse events and identifying patients with poor prognosis in aNSCLC immunotherapy. Incorporating genetic profiling into clinical practice may enable personalized toxicity monitoring and enhance treatment safety using precision medicine.