Abstract
Introduction Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have emerged as promising treatments for advanced NSCLC patients without actionable mutations. However, predicting treatment response remains challenging, especially in second-line settings. Although PD-L1 is the only validated biomarker, additional prognostic tools are needed. Systemic inflammation markers such as the neutrophil-to-lymphocyte ratio (NLR) show potential but remain underused. Myeloid-derived suppressor cells (MDSCs), linked to immunotherapy resistance, are associated with increased splenic volume. Therefore this study introduces a splenic index score, combining pre-immunotherapy splenic volume and NLR, to evaluate its prognostic value in NSCLC patients treated with nivolumab in the second-line setting. We analyzed 50 patients with metastatic non-small cell lung cancer (NSCLC) who received nivolumab as second-line or later therapy. Baseline splenic volume and neutrophil-to-lymphocyte ratio (NLR) were assessed using imaging and laboratory data prior to nivolumab initiation. The Splenic Index Score for each patient was calculated using the formula: (baseline splenic volume) × (NLR). Additionally, we evaluated the impact of other factors, including body mass index (BMI), tumor PD-L1 expression, Eastern Cooperative Oncology Group (ECOG) performance status, and sites of metastasis. The median Splenic Index score was 877.3 (range: 180-4830). A higher Splenic Index score was significantly associated with worse overall survival (OS) and progression-free survival (PFS) (p = 0.001 and p = 0.03, respectively). Specifically, patients with a high Splenic Index score had a median PFS of 3 months, compared to 8 months in those with a low Splenic Index score (HR 1.96, 95% CI 1-3.7, p = 0.03). Similarly, the median OS was 4 months for patients with a high Splenic Index score, while it was 15 months for those with a low score (HR 3.5, 95% CI 1.6-7.3, p = 0.001). Baseline splenic volume, basal NLR, and tumor PD-L1 expression were also evaluated; however, no significant differences in PFS or OS were observed for these parameters. Our study demonstrates that the splenic index score, derived from combining radiological and peripheral inflammatory biomarkers, serves as a predictive tool for progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients receiving second-line nivolumab therapy.