Risk of Venous and Arterial Thromboembolism in Patients With Cancer Receiving Immune Checkpoint Inhibitors

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In a single-institution retrospective analysis reported in the journal Blood, Moik et al found a substantial risk of thromboembolic events in patients receiving immune checkpoint inhibitor therapy for cancer, as well as an increased risk of mortality among those experiencing venous thromboembolism.

Study Details

The study included data from 672 patients treated with immune checkpoint inhibitors at the Medical University of Vienna between 2016 and 2018. The most common tumor types were melanoma (30.4%), non–small cell lung cancer (NSCLC; 24.1%), renal cell carcinoma (11.0%), and head and neck squamous cell carcinoma (10.4%). Disease stage was III in 11.8% of patients and IV in 85.8%. The most commonly used immune checkpoint inhibitors were nivolumab (42.0%), pembrolizumab (40.0%), ipilimumab (6.7%), and nivolumab/ipilimumab (6.0%). Prior treatment included chemotherapy in 56.1%, radiotherapy in 47.6%, and surgical removal of the primary tumor in 53.1%.

Key Findings

Over a median follow-up of 8.5 months (interquartile range = 7.6–9.6 months), a total of 47 cases of venous thromboembolism were observed, with a cumulative incidence of 12.9% (95% confidence interval [CI], 8.2%–18.5%) during immune checkpoint inhibitor therapy. A total of nine cases of arterial thromboembolism were observed, with a cumulative incidence of 1.8% (95% CI = 0.7%–3.6%). The most frequent types of venous thromboembolism were pulmonary embolism (n = 18) and deep-vein thrombosis (n = 17). Arterial thromboembolism events consisted of acute coronary syndrome in four patients, ischemic stroke in three, and acute vascular occlusion in two.

Patients with venous thromboembolism had significantly poorer overall survival vs those without venous thromboembolism (transition hazard ratio [HR] = 3.09, 95% CI = 2.07–4.60). Median overall survival after occurrence of venous thromboembolism was 11.6 months compared with 25.5 months in those without venous thromboembolism (P < .001). Venous thromboembolism was also associated with poorer progression-free survival (transition HR = 3.63, 95% CI = 2.47–5.36). Arterial thromboembolism was not associated with poorer overall survival (transition HR = 0.79, 95% CI = 0.25–2.48) or progression-free survival (transition HR = 0.64, 95% CI = 0.16–2.57),

Rates of venous thromboembolism were generally comparable among tumor types (eg, 12.9% in melanoma, 11.7% in NSCLC, 4.9% in renal cell carcinoma, and 8.7% in head and neck cancer), with a significantly elevated risk observed only for patients with gynecologic cancer (4 of 18, 26.9%) vs other cancers. Rates of venous thromboembolism were also generally comparable among immune checkpoint inhibitors (eg, 9.8% with nivolumab, 13.9% with pembrolizumab, 13.6% with ipilimumab monotherapy, and 19.9% with atezolizumab [n = 30], with no significant differences among these agents). No cases were observed among 40 patients receiving nivolumab/ipilimumab or 6 receiving avelumab.

History of venous thromboembolism was associated with greater risk of venous thromboembolism during treatment (subdistribution HR = 3.69, 95% CI = 2.00–6.81). Distant metastasis was associated with a nonsignificant increased risk (subdistribution HR = 1.71, 95% CI = 0.62–4.73).

No association of venous thromboembolism with Eastern Cooperative Oncology Group performance status, Charlson comorbidity index, or Khorana score was observed.  

The investigators concluded: “…Patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially [venous thromboembolism]. Furthermore, [venous thromboembolism] occurrence was associated with increased mortality.”

Cihan Ay, MD, of the Department of Medicine I, Medical University of Vienna, is the corresponding author for the Blood article.

Disclosure: The study was supported by the Anniversary Fund of the Austrian National Bank and the Austrian Science Fund. For full disclosures of the study authors, visit

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