# 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

## TL;DR

A low-cost blood test called SIII can predict survival in cancer patients receiving immune therapy, with both initial levels and changes during treatment being important.

## Contribution

This study demonstrates that baseline and on-treatment changes in SIII significantly predict overall survival in patients receiving immune checkpoint inhibitors.

## Key findings

- Lower baseline SIII is linked to improved overall survival in patients receiving immune checkpoint inhibitors.
- An increase in SIII during treatment is associated with reduced overall survival.
- Patients with low baseline SIII and a decline during treatment had the longest survival.

## 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.

Graphical AbstractFor image description, please refer to the figure legend and surrounding text.