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

Fatma Pınar Acar¹Caner Acar¹Damla Gunenc²Çağlar Arısoy³Aslı Ece Solmaz³Aslı Geçgel¹Haydar Çağatay Yüksel¹Gökhan Şahin¹Oğuzcan Özkan¹Zeynep Sıla Gökdere¹Nilay Duman⁴Burçak Karaca^1*

• ¹Division of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, Türkiye
• ²Division of Medical Oncology, Hatay Education and Research Hospital, Hatay, Türkiye
• ³Department of Medical Genetics, Ege University Medical Faculty, Izmir, Türkiye
• ⁴Deparment of Dermatology, Ege University Medical Faculty, Izmir, Türkiye

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.