Dr Saad on the Potential Predictive Value of IL7 SNPs in RCC

Eddy Saad, MD, MSc, postdoctoral research fellow, Dana-Farber Cancer Institute, discusses results from a study characterizing the association between a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL-7) gene and immune-related adverse effects (AEs), highlighting how this may inform treatment decision-making for select patients with renal cell carcinoma (RCC) who have received treatment with immune checkpoint inhibitors (ICIs).

Results revealed that the presence of an IL-7 single nucleotide polymorphism (SNP) is associated with an increased risk of immune-related adverse effects (irAEs) in patients receiving PD-1 inhibitors, such as nivolumab (Opdivo) and pembrolizumab (Keytruda). Saad explained that this association was not observed in patients treated with non-ICI therapies, like everolimus (Afinitor). Moreover, the presence of the IL-7 SNP did not correlate with differences in treatment outcomes or survival among patients treated with checkpoint inhibitors in either of the trials. These findings are significant as they suggest a potential genetic biomarker for predicting irAEs in patients undergoing ICI therapy, which could help clinicians better manage and personalize treatments.

Currently, there are no clinically available biomarkers to identify patients at risk for irAEs, making this discovery potentially transformative for cancer care, Saad begins. If validated in further studies, the IL-7 SNP may guide clinical decision-making by identifying patients who have the potential to benefit from preemptive strategies to mitigate irAEs, Saad states. For instance, patients identified as SNP carriers may receive an immunosuppressive regimen alongside their ICI therapy or have their treatment regimen adjusted to minimize the risk of irAEs, he explains.

The next steps involve advancing this research into a phase 3 clinical trial to confirm these findings and explore the clinical utility of using the IL-7 SNP as a predictive biomarker, Saad continues. Additionally, ongoing research aims to elucidate the biological mechanisms by which this germline variant contributes to irAEs, he says. However, understanding these mechanisms has proven challenging, partly because replicating these findings in model organisms such as mice has been difficult, Saad notes. Researchers are currently focused on identifying the specific immune cells involved in this association, which could provide insights into the underlying pathways and reveal new therapeutic targets, he details.

By uncovering the mechanisms at play and potentially identifying new therapeutic targets, this research could lead to more tailored and safer cancer immunotherapy options, improving outcomes for patients who are at higher risk for irAEs, Saad continues.