Risk Factors for Developing Venous Thromboembolism in Patients With Advanced ALK-Rearranged NSCLC

Introduction Patients with NSCLC have an increased risk of developing venous thromboembolism (VTE), a condition associated with a poorer prognosis. Those with ALK rearrangements have a three- to five-fold higher risk of VTE than those with other oncogenic drivers. This study aimed to investigate the incidence, risk factors, and impact of VTE on overall survival. Methods We retrospectively analyzed patients with advanced ALK-positive NSCLC treated at Karolinska University Hospital from 2009 to 2021. VTE events were recorded from 90 days before histologic cancer diagnosis to death or end of follow-up. The impact of VTE on survival was assessed using a time-dependent Cox model, and risk factors were evaluated using Fine-Gray competing risk regression. Results A total of 97 patients were included, of whom 35 (36.1%) developed VTE. Pulmonary embolism accounted for 24 cases (68.6%), with 16 events (45.7%) occurring more than 6 months after treatment initiation. The median time from diagnosis to the first clot was 167 days. Patients with VTE had a 3.43-fold increased risk of death. Competing risk regression analysis revealed that the presence of baseline adrenal metastasis (hazard ratio [HR] = 2.92, 95% confidence interval [CI]: 1.19–7.16), leukocyte count more than 11 × 10 9 /L (HR = 3.74, 95% CI: 1.91–7.31), and hemoglobin less than 10 g/dL (HR = 5.18, 95% CI: 2.07–12.94) significantly increased VTE risk, whereas albumin more than or equal to 3.5 g/dL reduced the risk (HR = 0.24, 95% CI: 0.10–0.56). Conclusion In advanced ALK-positive NSCLC, baseline adrenal metastases, leukocytosis, and anemia were associated with increased VTE risk and may warrant heightened clinical vigilance.