Cancer-associated VTE: can evidence for DOACs be extrapolated to haematological cancers?

Cancer care

By Dave Levitan

1 Mar 2021

Direct oral anticoagulants (DOACs) have changed the management of venous thromboembolism (VTE). In recent years their use has extended to the realm of cancer-associated VTE (CAT), but experts warn that a paucity of trial data in that setting should breed caution in the care of patients with haematological malignancies.

“Given the escalated risk of VTE in patients with haematological malignancies, it is important that changes to treatment paradigms are based on robust evidence,” wrote authors led by Dr Richard Buka, of the University of Birmingham, in a letter in the British Journal of Haematology.

Cancer in general raises the risk of thrombosis sevenfold, and patients with haematological malignancies are at the highest risk of any type of cancer. Until very recently, the standard of care for CAT has been low-molecular-weight heparin (LMWH), based on results of the 2003 CLOT study which showed benefit compared with a coumarin.

However, four phase III randomised trials on the use of DOACs in CAT have been published in the last two years (CARAVAGGIO, ADAM-VTE, HOKUSAI-VTE, and SELECT-D), leading to a NICE recommendation for their use as a first option in CAT.

Unfortunately, those trials offer only sparse evidence for the use of DOACs specifically in haematological malignancies. Though the trials included a total of 2,898 patients in total, only 257 patients were included in the broad category of haematological malignancies.

“Additionally, the haematological malignancies encompass a wide range of pathologies that have differential effects on the risk of VTE,” the authors wrote. “Patients with myeloma for example are particularly at risk of VTE during treatment with immunomodulatory drugs such as thalidomide.”

The four DOAC trials likely had fewer than 50 patients with multiple myeloma. There are likely even fewer with acute leukaemias; the CARAVAGGIO trial of apixaban explicitly excluded any patients with acute leukaemia, and in general there were exclusions based on levels of thrombocytopenia and anaemia.

“We are therefore of the opinion that given the high risk of thrombosis in patients with various haematological malignancies, and the stark paucity of data for safety and efficacy, the DOACs should be used with caution,” Dr Buka and colleagues wrote.

It is important to remember that LMWH is known to be a safe and effective treatment, with few drug interactions. Still, the authors added that DOACs do have efficacy for treatment of VTE in patients with haematological malignancies. Furthermore, the risk of dying from VTE or major bleeding in the various trials has been very low, with high rates of patients dying from their underlying disease.

“A trial of DOACs versus LMWH in patients with specific haematological malignancies would be ideal, but for now we are likely to have to make do with real‐world data,” the authors wrote.

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