(P 244) PREDICTIVE VALUE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO IN IMMUNOTHERAPY OUTCOMES IN ADVANCED SARCOMA

Objective: As immunotherapy is demonstrating promise in sarcoma, understanding patterns of response and identifying biomarkers for immune checkpoint inhibitors (ICI) remains challenging. We are expanding our prior cohort of patients to study potential clinical biomarkers and analyze responses to ICI based on treatment regimens and the neutrophil-to-lymphocyte ratio (NLR) to identify significant clinical factors in advanced sarcoma outcomes.

Methods: Patients in The Ohio State University Sarcoma Clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through December 31, 2023. Data included treatment regimen (single-agent ICI or ICI + combination) along with clinical covariates, specifically NLR at baseline. NLR was stratified as low NLR (< 5) or high NLR (≥5). Statistical analysis included log-rank tests and cox regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS).

Results: 192 patients met the inclusion criteria. The majority of patients were male (55%) and 83% were Stage 4 at the time of ICI start. ICI was typically initiated as a third-line regimen or beyond (52%). The majority of patients had received ICI only (57%) compared to 43% who had received ICI in combination (ICI+combination) with another modality (e.g., surgery, radiation, TKI). There were no differences seen in OS (p = 0.419) or PFS (p = 0.834) between patients who had received ICI only regimens or ICI+combination. However, this is confounded by many clinical variables in the ICI+combination group. Median OS was 60 weeks and median PFS was 40 weeks. However, we report significant differences in OS and PFS based on NLR. For all patients ion this cohort, those with a lower NLR had improved OS (p < 0.0001). Upon further analysis of different ICI regimens, the patients who had received ICI+combination or ICI with lower NLR at the start of treatment, OS were improved when compared to those who had a higher NLR (ICI+combination, p = 0.018; ICI, p< 0.0001). Notably, in patients who had a higher NLR at ICI start, there was improved OS if they had received ICI+combination (p = 0.039). Regarding PFS, in patients who had received any ICI regimen, there was improved PFS if NLR was low at ICI start (p=0.0002). Upon further analysis of different ICI regimens, there were no differences in PFS based on NLR if a patient had received ICI+combination. However, if a patient received ICI only, there was improved PFS if the NLR was low at ICI start (p=0.003). There were no differences in OS or PFS based on age, gender or histology.

Conclusion: This retrospective study provides evidence that NLR could serve as a clinical biomarker for predicting the response to ICI regimens in patients with advanced sarcoma. Further studies to validate these results are needed.