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Multiple factors were associated with an increased risk for venous thromboembolism (VTE) in hospitalized cancer patients with COVID-19, a registry-based cohort study found.

Pooled together, exposure to commonly used anti-cancer treatments in the 3 months prior to infection showed a 33% higher risk of VTE when compared with no systemic treatment during that time frame (adjusted risk ratio [aRR] 1.33, 95% CI 1.04-1.69), reported Shuchi Gulati, MD, MSc, of the University of California Davis Comprehensive Cancer Center in Sacramento, and colleagues.

As described in , only checkpoint inhibitors were significantly linked with a higher risk for VTE (aRR 1.45, 95% CI 1.01-2.07) when the researchers individually examined the different treatments of interest, which also included chemotherapy, endocrine therapy, VEGF inhibitors/tyrosine kinase inhibitors (TKIs), and immunomodulators.

Regardless of treatment exposure, patients with a history of VTE had a threefold higher risk of another event, while an increased risk was also observed among those with active and progressing cancer or a high-risk site of cancer. Black patients also had a higher risk of any thromboembolic event compared with white patients.

"These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer," wrote Gulati and co-authors.

When it came to cases of arterial thromboembolism (ATE), no association was observed between the treatments of interest pooled together or examined individually.

Occurrence of any thromboembolic event in this patient population was associated with high rates of mortality at 30 days (25%), admission to intensive care (46%), and mechanical ventilation (31%). And the risk for death following a thromboembolic event was numerically higher in patients exposed to the treatments of interest collectively and in those with a poor performance status or with active or progressing cancer.

"Patients with cancer have a higher baseline risk of VTE, which is further influenced by stage, type of cancer, and systemic anticancer therapies," the researchers noted.

"While COVID-19 has been shown to enhance the risk of TEEs [thromboembolic events] in patients with cancer, the contribution of systemic therapies has not been reported previously to our knowledge," they continued. "Additionally, drugs are often combined in the metastatic setting and could further enhance the risk of TEEs, especially if a patient is infected with SARS-CoV-2."

The study from Gulati and colleagues included 4,988 hospitalized patients with cancer and a documented SARS-CoV-2 infection enrolled in the COVID-19 and Cancer Consortium registry from March 2020 to December 2021. Of these 1,869 had received at least one treatment of interest in the 3 months preceding their COVID-19 and 3,119 patients had no exposure to systemic treatment during that time.

Included patients had a median age of 69 years, and a slight majority were male. About one-fifth of patients were Black, 16% were Hispanic, and 51% were white. About half were current or former smokers and 36% had a body mass index of 30 or above. About 20% were on anticoagulation prior to hospital admission, and 30% were taking aspirin, mostly low-dose.

Less than a third (31%) had metastatic disease, 44% had active cancer, 11% had a history of VTE, and 34% had a high risk for VTE based on their Khorana score. High-risk cancers included lymphoma (n=422) and those of the lung (n=472), kidneys (n=199), uterus (n=157), bladder (n=148), pancreas (n=81), ovaries (n=68), stomach (n=55), esophagus (n=38), and testicles (n=35).

Overall, thromboembolic events occurred in 11% of the population, VTE in 7% and ATE in 4%. Incidence of VTE was higher across the treatment types examined -- checkpoint inhibitors (12%), chemotherapy (10%), VEGF inhibitors/TKIs (10%), immunomodulators (8%), and endocrine therapy (7%) -- compared with the no-treatment group (6%), though none aside from checkpoint inhibitors reached significance:

• Chemotherapy: aRR 1.27 (95% CI 0.99-1.62)
• Endocrine therapy: aRR 1.21 (95% CI 0.84-1.74)
• VEGF inhibitors/TKIs: aRR 1.32 (95% CI 0.93-1.86)
• Immunomodulators: aRR 1.37 (95% CI 0.76-2.48)

ATE incidence across the different treatment groups was the same or lower compared with the reference group (5%): endocrine therapy (5%), immunomodulators (4%), chemotherapy (3%), checkpoint inhibitors (2%), and VEGF inhibitors/TKIs (2%).

Regardless of treatment exposure, preadmission use of antiplatelets (aRR 1.62, 95% CI 1.04-2.53) or low-dose aspirin (aRR 1.49, 95% CI 1.08-2.06) were associated with an increased risk for ATE, possibly due to "a higher underlying risk of arterial clots in patients receiving these drugs," the researchers suggested.

Limitations included those common in registry-based studies, including the potential for bias and missing data for certain variables. Also, while the data span the pre- and post-vaccine era, researchers were unable to assess associations between vaccines and thromboembolic events as few patients (3%) had received at least one dose of vaccine.

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