The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study

Background Thrombosis is common among patients with cancer. Primary thromboprophylaxis guided by the Khorana score is endorsed by guidelines but recommendations rely mainly on data from patients treated with chemotherapy. Objectives To explore if the Khorana score could risk stratify patients with cancer treated with immune checkpoint inhibitors according to risk of venous and arterial thrombosis. Patients/Methods The study population and Khorana score were defined using administrative Danish health registries. The primary outcome was 6-month risk of venous thromboembolism after initiation of checkpoint inhibitor treatment. Secondary outcomes were arterial thrombosis and any thromboembolic event. Death was considered a competing risk event. Results Among 3946 patients with cancer initiating checkpoint inhibitor treatment without other indications for anticoagulation, the overall 6-month incidence of venous thromboembolism was 2.6% (95% confidence interval [CI]: 2.1-3.1). Risks were 2.1% (95% CI: 1.5-3.0), 2.6% (95% CI: 2.0-3.4), and 3.7% (95% CI: 2.1-5.9) in low (score 0), intermediate (score 1-2), and high risk (score >= 3) Khorana categories, respectively. Among patients eligible for primary thromboprophylaxis according to guidelines (Khorana score >= 2), risk of venous thromboembolism was 4.1% (95% CI: 3.1-5.4). Higher Khorana risk category was also associated with higher 6-month risk of both arterial thrombosis and any thromboembolic events. Conclusions The Khorana score was able to risk stratify patients with cancer treated with immune checkpoint inhibitors according to 6-month risk of thromboembolic events. Risks of venous thromboembolism were lower than in randomized thromboprophylaxis trials, thus questioning the absolute benefit of routine primary thromboprophylaxis in an unselected population of patients treated with immune checkpoint inhibitors.

Automated summary

The Khorana score can stratify patients with cancer treated with immune checkpoint inhibitors according to the 6-month risk of thromboembolic events. The risk of venous thromboembolism in this population was lower than in randomized thromboprophylaxis trials, which raises questions about the absolute benefit of routine primary thromboprophylaxis for these patients. Higher Khorana risk categories were also associated with a higher 6-month risk of arterial thrombosis and any thromboembolic events.