Overall survival by baseline and on-treatment systemic immune-inflammation index in patients with advanced cancer receiving immune checkpoint inhibitors: a large single-centre cohort study

Abstract The Systemic Immune-Inflammation Index (SIII; neutrophils/lymphocytes × platelets) is a low-cost biomarker proposed to predict outcomes with immune checkpoint inhibitors (ICIs). This study evaluated associations of baseline and early on-treatment changes in SIII with overall survival (OS) for common ICI regimens. Patients with advanced cancer treated with ICIs at a UK centre were categorized by baseline SIII (above vs. below the median) and by changes at 3–6 weeks (increase/decrease). OS was analysed using Kaplan–Meier estimates. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated using multivariable Cox regression. Among 2578 patients included, 1514 deaths occurred over a median follow-up of 2.6 years. Common regimens included pembrolizumab or atezolizumab with (15.9%) or without chemotherapy (13.9%) for NSCLC, and nivolumab plus ipilimumab for melanoma (12.6%). Lower baseline SIII was associated with improved OS (28.1 vs. 11.1 months; aHR 0.56, 0.50–0.62), with a weaker association observed in those receiving ICI-targeted therapy combinations. An on-treatment increase in SIII was linked to reduced OS (16.8 vs. 21.5 months; aHR 1.33, 1.18–1.49). Patients with low baseline SIII and an on-treatment decline had the longest OS (33.2 months), whereas those with high baseline SIII and an on-treatment increase had the shortest (8.2 months; aHR 2.88, 2.41–3.44; interaction between baseline and on-treatment SIII P < 0.001). SIII is a low-cost, readily available biomarker. Both baseline SIII levels and on-treatment changes in SIII are significantly associated with OS. SIII may help identify patients who could benefit from closer monitoring or treatment adjustments.