Predicting Immune-Related Adverse Events in Patients with Melanoma: The Role of Interleukin-7 rs16906115 Polymorphism and Lymphocyte Dynamics

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of malignant melanoma; however, they are frequently associated with immune-related adverse events (irAEs). Emerging evidence suggests that genetic predispositions, including interleukin-7 (IL-7) gene variants, may influence the risk of these toxicities. In this single-centre retrospective study, we investigated the potential utility of IL-7 rs16906115 polymorphism and lymphocyte stability index (LSI) in predicting susceptibility to irAEs among 96 melanoma patients treated with ICIs. Genotyping revealed a minor allele frequency of 8.3% for rs16906115. Logistic regression analysis indicated that carriers of the minor allele had a significantly increased risk of all-grade irAEs compared to reference allele carriers (adjusted OR: 3.93; 95% CI: 1.13–13.64; p = 0.031). Subgroup analyses revealed a significant increase in risk across endocrine, non-cutaneous, multiple, low-grade, and early onset (< 3 months) irAEs. While neither baseline lymphocyte count nor LSI predicted overall irAE incidence, an elevated LSI emerged as a key risk factor for early steroid-requiring irAEs (adjusted OR: 3.79; 95% CI: 1.14–12.61; p = 0.030). These findings from a Turkish cohort corroborate earlier European studies suggesting that rs16906115 minor allele carriage may be a genetic risk factor for irAEs. Furthermore, LSI may serve as a dynamic biomarker for predicting early steroid-requiring irAEs. Prospective multicentre studies among diverse populations are warranted to validate these findings.This study was supported by the Turkish Society of Medical Oncology (TTOD), although the organization is not listed in the Zenodo funding registry.