Incidence and risk factors of venous and arterial thromboembolism events in lung cancer patients treated with immune checkpoint inhibitors.

Background: Thromboembolism (TE), which comprises venous thromboembolism (VTE) and arterial thromboembolism (ATE), represents a significant cause of mortality in patients with lung cancer. It is also associated with considerable morbidity and increased healthcare expenditure. Previous studies have indicated that systemic therapies, including surgery, chemotherapy, radiotherapy, anti-angiogenic therapy, and immunotherapy, can elevate the risk of VTE in patients with lung cancer. However, the risks associated with immune checkpoint inhibitors (ICIs) remain inadequately understood, particularly concerning ATE. This single-center retrospective study aims to assess the incidence of VTE/ATE in a cohort of lung cancer patients undergoing treatment with ICIs, while concurrently identifying potential clinical risk factors. Methods: A single-center retrospective analysis was conducted of 504 lung cancer patients who received ICIs from January 2019 to December 2022. We examined clinical predictors of TE among all patients. Accordingly, we have defined a predefined critical risk window-from the administration of first ICI dose to 4 weeks after the final dose-established to specifically capture treatment-related thromboembolic events, including VTE and ATE. Follow-up data are obtained through electronic medical records and telephone communication as well as inpatient and outpatient records. Cumulative incidences and risk factors of TE were assessed within a competing-risk framework. Results: During a mean follow-up period of 27.2 months, TE occurred in 104 out of 504 individuals (20.6%) while on immunotherapy. Among those with TE, 90.4% developed VTE (n = 94), 3.9% experienced ATE (n = 4), and 5.8% had both VTE and ATE (n = 6). The cumulative incidence of TE events at 3, 6, 12 and 24 months were 10.1%,15.7%,19.7% and 20.6%, respectively. For VTE events specifically, the cumulative incidence at these same time points were 9.1%,14.1%,17.5% and 18.7%, respectively. Additionally, the cumulative incidence of ATE events at 3, 6 and 12 months were 1.0%,1.6% and 2.0%, respectively. According to multivariate analysis, four variables were identified as independently associated with TE: age-adjusted Charlson comorbidity index (ACCI) > 8(HR 1.6, 95% CI 1.1-2.3, p = 0.027), the presence of a central venous catheter (CVC) (HR 2.2, 95% CI 1.2-3.9, p = 0.013), D-dimer >0.5 mg/L (HR 1.5, 95% CI 1.0-2.3, p = 0.042), and brain metastases (HR 2.0, 95% CI 1.3-3.1, p = 0.003). Conclusion: In this study, immune checkpoint inhibitors (ICIs) are associated with a high incidence of VTE in patients with lung cancer, as well as a notable incidence of ATE. In particular, 5.8% of patients with TE experienced both VTE and ATE. This study corroborates the identified risk factors for TE in lung cancer patients undergoing immunotherapy. Targeted thromboprophylaxis may alleviate the burden of TE in this population.