Neutrophil-to-lymphocyte ratio as a clinical biomarker for immune checkpoint inhibitor response in advanced sarcoma.

Abstract

11543 Background: As immunotherapy gains traction in sarcoma treatment, identifying biomarkers and understanding patterns of response to immune checkpoint inhibitors (ICI) remain critical. We expanded a prior cohort to investigate clinical factors, including the neutrophil-to-lymphocyte ratio (NLR) and its changes, in predicting outcomes such as overall survival (OS) and progression-free survival (PFS) in advanced sarcoma. Methods: Patients from The Ohio State University Sarcoma Clinics (2015–2023) were included in a retrospective ICI database. Data included treatment regimens (single-agent ICI or ICI+combination therapy) and clinical variables, particularly baseline and post-treatment NLR stratified into low ( < 5) or high (≥5). Survival outcomes were analyzed using log-rank tests and Cox regression to assess OS and PFS. Results: A total of 192 patients met the inclusion criteria. Most were male (55%), and 83% had Stage 4 disease at ICI initiation. ICI was started as a third-line or later therapy in 52% of cases. The majority received single-agent ICI (57%), while 43% underwent ICI+combination therapy with other modalities (e.g., surgery, radiation, TKI). OS and PFS were similar between single-agent ICI and ICI+combination groups (OS: p = 0.419; PFS: p = 0.834), though clinical variables in the ICI+combination group may confound results. Median OS was 60 weeks, and median PFS was 40 weeks. Significant differences in OS and PFS were associated with NLR. Patients with lower NLR had improved OS (p < 0.0001). Among those with higher NLR at ICI initiation, OS improved with ICI+combination therapy (p = 0.039). After the first ICI cycle, the OS benefit persisted for patients with high NLR (p < 0.0001), regardless of treatment type. However, survival did not differ by treatment modality or by changes in NLR from baseline (p = 0.710). For PFS, patients with low NLR at ICI initiation had improved outcomes (p = 0.0002). Further analysis showed no PFS differences by NLR in the ICI+combination group. After the first cycle, the PFS benefit for low NLR persisted (p = 0.0006). Conversely, an increased NLR ratio from baseline to the first cycle was linked to worse PFS (p = 0.003), particularly in the ICI+combination group (p = 0.0029) but not in single-agent ICI (p = 0.8630). OS and PFS were not influenced by age, gender, or histology. Conclusions: NLR is a promising clinical biomarker for predicting response to ICI in advanced sarcoma. Low baseline NLR predicts improved OS and PFS, while changes in NLR may indicate progression risk. These findings warrant further prospective validation. Variable OS (p-value) PFS (p-value) Low vs. High NLR <0.0001 0.0002 High NLR + Combination 0.039 0.834 NLR Change (Baseline) 0.710 0.003 NLR values.