Dr Saad on the Association Between IL-7 SNPs and Immune-Related AEs in RCC

Eddy Saad, MD, MSc, postdoctoral research fellow, Dana-Farber Cancer Institute, discusses findings from a study characterizing and validating the association between a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL-7) gene and immune-related adverse effects (AEs) in 2 prospective, randomized, phase 3 trials of patients with cancer, including renal cell carcinoma (RCC), who received immune checkpoint inhibitors (ICIs).

This study included data from the phase 3 CheckMate 025 trial (NCT01668784) investigating nivolumab (Opdivo) vs the mTOR inhibitor everolimus (Afinitor) in patients with advanced RCC. Investigators also analyzed data from the phase 3 INTR@PID LUNG 037 trial (NCT03631706), which evaluated bintrafusp alfa vs pembrolizumab (Keytruda) in patients with advanced non–small cell lung cancer.

Across both studies, investigators found that the presence of an IL-7 SNP was associated with immune-related AEs in patients who received the PD-1 inhibitors nivolumab and pembrolizumab, Saad says. However, the presence of this SNP was not associated with immune-related AEs in the patients who received non-ICI agents, such as everolimus, Saad explains. This finding indicates that the relationship between the presence of SNPs and the incidence of immune-related AEs is limited to SNP carriers who receive ICIs, he notes. The IL-7 SNP was also associated with recurrent immune-related AEs in the ICI arms of the CheckMate 025 trial.

Moreover, the presence of an IL-7 SNP was not associated with treatment or survival outcomes with checkpoint inhibitors in either trial, Saad emphasizes. In CheckMate 025, the differences in PFS and OS outcomes with nivolumab between the IL-7 SNP carriers and SNP wild-type patients were not statistically significant (PFS, log-rank P = .47; OS, log-rank P = .74). Therefore, this SNP may be used as a biomarker to predict which patients may develop immune-related AEs from ICIs, Saad reports. Patients who are at higher risk of developing these AEs may then be considered for other types of treatment, Saad concludes.