Increased incidence of venous thromboembolism with cancer immunotherapy

Background: Cancer immunotherapy is associated with several immune-related adverse events, but the relationship between immunotherapy and venous thromboembolism has not been thoroughly studied. Methods: We conducted a retrospective cohort study of 1,686 individuals who received immunotherapy for a variety of malignancies to determine the incidence of venous thromboembolism and the effect of venous thromboembolism on survival. To examine the potential role of inflammation in venous thromboembolism, we also profiled immune cells and plasma cytokines in blood samples obtained prior to initiation of immunotherapy in a sub-cohort of individuals treated in clinical trials who subsequently did (n = 15) or did not (n = 10) develop venous thromboembolism. Findings: Venous thromboembolism occurred while on immunotherapyin 404 of 1,686 individuals (24%) and was associated with decreasedoverall survival (hazard ratio, HR = 1.22 [95% confidence interval (CI),1.06- 1.41], p < 0.008). Individuals who developed venous thromboembolismhad significantly higher pretreatment levels of myeloid-derivedsuppressor cells (5.382 G 0.873 versus 3.341 G 0.3402, mean G SEM,p = 0.0045), interleukin 8 (221.2 G 37.53 versus 111.6 G 25.36,mean G SEM, p = 0.016), and soluble vascular cell adhesion protein 1(1,210 G 120.6 versus 895.5 G 53.34, mean G SEM, p = 0.0385). Conclusions: These findings demonstrate that venous thromboembolism is an underappreciated and important immune-related adverse event associated with cancer immunotherapy and may implicate an interleukin-8 and myeloid-derived suppressor cell-driven pathway in pathogenesis.