Systemic Inflammation and Risk of Thromboembolism, Mortality, and Treatment Response in Patients With Cancer Receiving Immune Checkpoint Inhibitors

BACKGROUND: Immune checkpoint inhibitors (ICI) are widely used in cancer therapy, but biomarkers for thromboembolic risk, treatment response, and survival remain limited. We evaluated the association of systemic inflammatory indices with these clinical outcomes. METHODS: In this retrospective cohort study, 580 ICI-treated patients at the Medical University of Vienna, Austria, were included. Inflammatory indices including neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), lymphocyte-monocyte-ratio (LMR), systemic immune-inflammation-index (SII) and C-reactive-protein-albumin-ratio (CAR) were calculated at ICI-start and longitudinally within 3 months. Co-primary outcomes were risk of venous thromboembolism (VTE), assessed using competing risk analysis, and overall- and progression-free-survival (OS/PFS), evaluated with Cox regression, whereas longitudinal biomarker dynamics were analysed using time-dependent analyses. RESULTS: Higher baseline NLR (HR 1.65, 95% CI: 1.28-2.12), CAR (HR 1.99, 95% CI: 1.67-2.38), and SII (HR 1.18, 95% CI: 1.00-1.39) were independently associated with shorter OS, while higher LMR (HR 0.44, 95% CI: 0.30-0.67) was associated with longer survival. For PFS, elevated NLR (HR 1.29, 95% CI: 1.05-1.57), higher PLR (HR 1.18, 95% CI: 1.00-1.39), lower LMR (HR 0.57, 95% CI: 0.43-0.70), and higher CAR (HR 1.42, 95% CI: 1.28-1.62) predicted poorer outcomes. None of the indices at treatment start were associated with VTE, yet doubling of levels within 3 months indicated higher VTE risk for PLR (sub-distribution hazard ratio [SHR]: 3.03 95% confidence interval [CI]: 1.05-8.08) and a borderline-significant association for CAR (SHR: 2.02, 95% CI: 0.89-4.60). CONCLUSION: We found that selected inflammatory indices were associated with poor OS and PFS in ICI-treated patients, and longitudinal dynamics might identify patients at higher risk for VTE.