Neutrophil to Lymphocyte Ratio as a Biomarker for the Prediction of Cancer Outcomes and Immune-Related Adverse Events in a CTLA-4-Treated Population

Abstract

Background/Objectives: Immune-related adverse events (irAEs) triggered by immune checkpoint inhibitor therapy (ICI) have been paradoxically associated with both significant morbidity and improved cancer outcomes. While predictive markers for irAEs have been studied in the PD-1 blockade, less is known for their role in CTLA-4 inhibition. This study aims to fill this gap by evaluating NLR and irAE incidence in a CTLA-4-treated population. Methods: This study is a single-center retrospective cohort study investigating 111 patients treated with CTLA-4 inhibition (ipilimumab) to assess associations for baseline low NLR values with cancer outcomes and irAE type and incidence. Patient charts were manually reviewed by a single physician, and unclear clinical events were assessed by a second physician reviewer. Results: In this cohort, the occurrence of more than one irAE presentation was associated with an improved cancer outcome, OR 1.48 (1.02, 2.15). When stratified by organ-specific manifestation, only endocrinologic irAEs were associated with improved cancer outcome, OR 2.82 (1.19, 6.67). A low baseline NLR was statistically significantly associated with an increased incidence of irAEs of any type, OR 4.34 (1.73, 10.9). Conclusions: These data show that irAE occurrence in cancer patients treated with CTLA-4 inhibition is associated with improved cancer outcomes, similar to that previously seen with PD-1 inhibition. It also suggests that the NLR may serve as a practical peripheral biomarker to predict both cancer response and odds of irAEs in patients treated with CTLA-4 inhibition. This low-cost and widely available tool could provide additional information for modeling cancer outcomes.