Thrombotic complications in patients treated with immune checkpoint inhibitors: a retrospective study of incidence, risk factors, and survival outcomes.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer outcomes across multiple malignancies. However, emerging evidence suggests that thrombotic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE) are serious complications that may negatively affect survival. This study aims to determine their incidence, identify independent risk factors, and evaluate effects on outcomes and survival. METHODS: We retrospectively reviewed adult patients treated with ICIs at a tertiary academic center. Thrombotic events were classified as VTE or ATE occurring from ICI initiation through follow-up. Clinical, laboratory, and treatment-related variables were collected. Kaplan-Meier methods and multivariable Cox proportional hazards models were used to evaluate survival impact and identify independent predictors. RESULTS: Among 750 patients treated with ICIs, 125 (16.6%) thrombotic events occurred over a median follow-up of 25 months. Of these events, 105 (84.0%) were VTE and 20 (16.0%) were ATE. Of all thrombotic events, 38% occurred within the first 6 months, 56% within 12 months, 67% within 18 months, and 74% within 24 months. Independent predictors of TE included prior VTE (HR 1.84, 95% CI 1.12-3.01; p = 0.015), lower baseline hemoglobin (HR 0.88, 95% CI 0.80-0.99; p = 0.036), and older age at immunotherapy initiation (HR 1.07 per year increase, 95% CI 1.04-1.11; p < 0.001).Thrombotic events were associated with significantly worse overall survival (OS) (log-rank p < 0.001) and remained independently associated with mortality in multivariable analysis (HR 2.55, 95% CI 1.89-3.43; p < 0.001). Additionally, prior thrombotic events (HR 1.86, 95% CI 1.29-2.69; p = 0.001) and a Khorana score ≥2 (HR 1.31, 95% CI 1.13-1.50, p<0.001) were independently associated with worse OS. CONCLUSIONS: Thrombotic events are common in patients receiving ICIs and are independently associated with worse survival. Risk-based and personalized assessment of thrombotic events can help guide monitoring and management strategies.