# Hematological ratios, immune-related adverse events and mortality in patients treated with immune checkpoint inhibitors

## TL;DR

This study found that high inflammation-related blood cell ratios before treatment with immune checkpoint inhibitors are linked to higher mortality, but not to immune-related side effects.

## Contribution

The study is the first to show that pretreatment hematological ratios are not associated with immune-related adverse events but are linked to mortality in checkpoint inhibitor-treated patients.

## Key findings

- Pretreatment hematological ratios were not associated with immune-related adverse events.
- Higher tertiles of all hematological ratios were independently linked to increased mortality risk.
- NLR, PLR, NLPR, and SII showed significant adjusted hazard ratios for mortality.

## Abstract

Although immune checkpoint inhibitors improve survival in patients with malignancies, a substantial number of patients treated with these agents experience immune-related adverse events. It is unknown whether inflammation-related hematological ratios are associated with immune-related adverse events or mortality.

We aimed to investigate the association between pretreatment inflammation-related hematological ratios and the occurrence of immune-related adverse events and mortality in patients receiving checkpoint inhibitors.

Patients treated with checkpoint inhibitors within a tertiary hospital in the Netherlands were studied using routine care data between January 2013 and May 2020. Cox regression analysis was performed to assess the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes and platelets ratio (NLPR), and systemic immune-inflammation index (SII) and outcomes (immune-related adverse events or mortality).

Among 664 patients treated with checkpoint inhibitors, 397 (59.8%) patients developed an immune-related adverse event and 363 (54.7%) patients died during a median follow-up period of 17 months (interquartile range 7–30 months). Hematological ratios were not associated with immune-related adverse events. However, highest tertiles as compared with lowest tertiles of all hematological ratios were independently associated with mortality (NLR: adjusted hazard ratio (HR) 2.23, 95% CI 1.69–2.95; PLR: adjusted HR 1.88, 95% CI 1.43–2.47; NLPR: adjusted 1.59, 95% CI 1.22–2.06; SII: adjusted HR 2.33, 95% CI 1.77–3.08).

In this study, pretreatment inflammation-based hematological ratios were not associated with future immune-related adverse events in patients treated with checkpoint inhibitors. However, elevated hematological ratios were associated with an increased mortality risk.