Safety and efficacy of apixaban for routine thromboprophylaxis in myeloma patients treated with thalidomide‐ and lenalidomide‐containing regimens

For patients with malignancy, there is increasing evidence for the use of direct oral anticoagulants (DOACs) in the treatment of venous thromboembolism (VTE) (Raskob et al, 2018), but their role in routine thromboembolic prophylaxis remains unclear. One group at high risk of both arterial and venous thrombosis is those with myeloma, particularly when treated with immunomodulatory drugs (IMiDs), such as thalidomide or lenalidomide (Leleu, 2012). Current guidelines suggest risk-adapted thromboprophylaxis with aspirin, low molecular weight heparin (LMWH) or warfarin (Palumbo Leleu, 2012) and in the recent presentation of data from the UK Myeloma XI study, up to 11·8% of patients experienced thromboembolism, most of whom took thromboprophylaxis as recommended (Bradbury et al, 2017). Current agents therefore have limited efficacy and present significant practical barriers, such as the need for subcutaneous injection or monitoring of the International Normalised Ratio, which limit compliance (Kahn et al, 2012). DOACs are promising due to their convenience and are known to be highly effective in other settings. There is some phase II trial data supporting routine prophylaxis of apixaban in patients with malignancy (Levine et al, 2012), and the Hokusai study of edoxaban for treatment of cancer-associated thrombosis included some patients with haematological malignancies treated with immunomodulatory drugs (Raskob et al, 2018). Here we report on our use of apixaban in myeloma patients treated with IMiDs. We previously performed an audit of 56 consecutive myeloma patients treated with IMiD-containing regimens between 2013 and 2014. Six of 29 patients (20·7%) receiving thromboprohylaxis with aspirin had VTE, and of 27 patients treated with heparins, 2 (7·4%) had VTE. These rates are broadly comparable with data in the literature and represent significant patient morbidity. In November 2014 our policy was changed such that apixaban became the standard thromboprophylaxis; the effect of this change is reported here. Our aim was to assess the safety and efficacy of apixaban as thromboprophylaxis in patients with multiple myeloma undergoing first line therapy with IMID-containing regimens. Consecutive myeloma patients who presented between 1 November 2014 and 31 December 2016 and who underwent first-line therapy with IMiD-containing regimens were included in this retrospective study. All patients received apixaban 2·5 mg twice daily for the first 4 months of therapy or until treatment was completed – whichever was shorter, and for a maximum of 6 months (unless another indication for anticoagulation was present, such as atrial fibrillation). Most patients therefore received apixaban prophylaxis throughout treatment but apixaban was not co-prescribed if IMiD therapy continued beyond this time. Patients with severe renal failure (creatinine clearance <15 ml/min) or thrombocytopenia <50 × 109/l received alternative anticoagulants and were excluded from this study. Patients already taking warfarin were also excluded. The primary outcome was the occurrence of arterial or venous thromboembolism within 6 months of treatment initiation. The incidence of bleeding episodes was recorded as follows: major bleeding according to International Society on Thrombosis and Haemostasis criteria (Schulman NS and AM collected and analysed data, PREJ provided access to patient data, NPFS wrote the manuscript. All authors critically revised the paper and approved the final version. The authors have no conflicts of interest.