Patients with myeloma who receive treatment with immunomodulatory drugs (IMIDs) such as lenalidomide and thalidomide have an increased risk of venous thromboembolism (VTE), but standard options for VTE prophylaxis, including low-molecular-weight heparin (LMWH) and warfarin, also increase patients’ risk of bleeding. Apixaban, a direct oral inhibitor of factor Xa, has been proposed as an alternative to prophylactic anticoagulation based on research showing increased efficacy, without an increased bleeding risk, over enoxaparin in a variety of settings. However, research about the use of apixaban in the population of patients with myeloma treated with IMiDs is limited.
At the 2017 ASCO Annual Meeting, Brigitte Pegourie, MD, from Grenoble Alpes University Hospital in France, shared early results from a prospective pilot study of apixaban as VTE prevention in patients with myeloma who were receiving IMIDs as front-line (melphalan, prednisone, and thalidomide) or second-line treatment (lenalidomide plus dexamethasone).1 At the time of enrollment, all patients were asymptomatic for VTE. Eleven patients were receiving front-line therapy, and 93 had relapsed disease.
Between June 2014 and June 2016, 104 patients (mean age = 69.8 years) received apixaban 2.5 mg twice-daily for 6 months, and were monitored monthly for VTE (including pulmonary embolism [PE] and symptomatic proximal or distal deep vein thrombosis [DVT]), all proximal asymptomatic events, arterial thrombotic events, and bleeding events for 7 months.
Patients were on apixaban treatment for a median of 168 days (range = 163-171 days).
To contextualize the VTE risk reduction and safety associated with apixaban, Dr. Pegourie and colleagues compared rates of VTE recurrence in this pilot study with those reported in an earlier meta-analysis of different thromboprophylactic agents in patients with newly diagnosed or previously treated myeloma who were receiving thalidomide- or lenalidomide-based regimens.2 Based on these results, the incidences of events per 100 patient-months during the treatment period were expected to be: <2.1 percent symptomatic VTEs, <0.47 percent severe bleeding events, and <2.2 percent clinically relevant non-major bleeding events.
Overall, no pulmonary embolism or arterial cardiovascular events were reported, but two VTEs were recorded (an asymptomatic proximal DVT and a symptomatic distal DVT), for an incidence rate of 0.38 percent (95% CI 0.05-1.4) – well below the pre-specified limit, the researchers noted.
Twelve hemorrhagic events occurred, but only one of these was considered a “major” event, for incidence rates for severe bleeding and non-major bleeding of 0.19 percent (95% CI 0.04-1.1) and 1.9 percent (95% CI 0.9-3.5), respectively.
“Referring to the incidence of thromboembolic events in [the earlier] meta-analysis and to major hemorrhagic events in medical patients receiving apixaban in primary VTE prophylaxis, apixaban used in a preventive scheme seems to be efficient and safe in preventing VTE in myeloma patients treated with immunomodulator drugs,” the authors concluded.
The study is limited by the lack of a comparator arm and single-center design. Larger trials will need to compare apixaban directly with low-molecular-weight heparins, warfarin, and other VTE prophylactic regimens.
- Pegourie B, Pernod G, Karlin L, et al. Evaluation of an oral direct anti-Xa anticoagulant, apixaban, for the prevention of venous thromboembolism in patients with myeloma treated with IMiD* compounds: A pilot study (MYELAXAT). Abstract #8019. Presented at the 2017 ASCO Annual Meeting, June 5, 2017; Chicago, Illinois.
- Carrier M, Le Gal G, Tay J, et al. Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost. 2011;9:653-63.