Characterization of Age-Associated, Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Survival

SIMPLE SUMMARY: Older adults have a unique biology characterized by inflammation. Inflammation, however, is thought to affect the efficacy of immune therapies in patients with cancer, and there are currently no biomarkers to predict the response of older patients with cancer to immune checkpoint inhibitors (ICI). In this study, we explored the potential of two markers of inflammation (NLR: neutrophil-to-lymphocyte ratio, and SII: systemic immune-inflammatory index) in the blood to predict a response to ICI in patients ≥80 years old. We showed that lower levels of NLR and SII were significantly associated with a better response in patients ≥80 years, exclusively, and that low levels of SII were associated with prolonged survival independent of other clinicopathologic features. Pre-treatment levels of inflammatory markers are thus potential biomarkers that can be used to predict better response rates and survival in geriatric patients with cancer treated with ICIs. ABSTRACT: Background: Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help with patient selection. Methods: We built a multicenter, international retrospective study of 885 patients (<80 years: n = 417, 47.12%; ≥80 years: n = 468, 52.88%) with different tumor types treated with ICIs between 2011 and 2021 from 11 academic centers in the U.S. and Europe. The main outcome measures were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) stratified by age and circulating inflammatory levels (neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII)). Results: Patients ≥80 years with low NLR (NLR-L) and SII (SII-L) had significantly higher ORR (vs. high NLR [NLR-H], p < 0.01 and SII-H, p < 0.05, respectively). At median follow-ups (13.03 months), and compared to SII-H, patients with SII-L had significantly longer median PFS and OS in patients <80 (p < 0.001), and ≥80 years (p < 0.001). SII-L was independently associated with longer PFS and OS (HR: 0.61 and 0.62, respectively, p < 0.01). Conclusion: Lower inflammation pre-ICI initiation may predict an improved response and survival in geriatric patients with cancer.