Immune checkpoint inhibitors combined with chemotherapy enhance coagulation activation and elevate venous thromboembolism risk in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality. The combination of immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard first-line treatment, yet their effects on coagulation and thrombosis risk are not fully defined. The retrospective cohort study analyzed 218 NSCLC patients receiving either ICI plus chemotherapy (n=102) or chemotherapy alone (n=116). We compared objective response rate (ORR), disease control rate (DCR), key coagulation biomarkers (D-dimer, fibrinogen, fibrin degradation products [FDP], and plasmin-α₂ antiplasmin complex [PAP]), and venous thromboembolism (VTE) incidence between groups. Compared to chemotherapy alone, combination therapy had significantly higher ORR (50.98% vs. 31.03%, P=0.003) and DCR (84.31% vs. 72.41%, P=0.034). Following treatment, the combination group also showed significantly greater elevations in coagulation biomarkers: D-dimer (1.12±0.48 vs. 1.84±0.41 mg/L), fibrinogen (4.26±1.08 vs. 3.78±0.94 g/L), FDP (6.27±2.48 vs. 5.18±2.13 µg/mL), and PAP (1.28±0.46 vs. 1.02±0.41 µg/mL; all P<0.001). Moreover, VTE incidence was notably higher in the combination group (16.67% vs. 7.76%, P=0.043). While ICI-chemotherapy offers superior antitumor efficacy, it is associated with greater coagulation activation and an increased VTE risk compared to chemotherapy alone in NSCLC patients.