Apixaban for the prevention of thromboembolism in immunomodulatory‐treated myeloma patients: Myelaxat, a phase 2 pilot study

Abstract

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low‐molecular‐weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti‐Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan‐Prednisone‐Thalidomide in the first line, or Lenalidomide‐Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism—PE, or symptomatic proximal or distal deep vein thrombosis—DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide‐induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

“…Pergourie et al also recently presented data from the use of apixaban as prophylaxis in MM patients on IMiDs. Two events were reported among 140 patients receiving apixaban 2.5 mg twice daily over six months [97]. DOACs are substrates of P-glycoprotein and P450; therefore an important issue to note with their use compared to the other classes of drugs is the potential drug-drug interactions.…”

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents

“…Several studies have in fact shown a promising efficacy of the new oral anticoagulants (DOACs) in preventing thrombosis in cancer patients, including MM [40,49,51,55]. Recent studies also showed that apixaban, especially at low dose, was safe and effective for thromboprophylaxis in relatively small series of MM patients receiving an IMiD-containing regimen as first line treatment or for relapsed disease [53]. Therefore, although further studies are needed for evaluating the role of DOACs in VTE prophylaxis in MM patients and possible drug interactions between DOACs and specific myeloma treatment, including supportive medications, these drugs seem to be at least as effective as LMWH and are an attractive alternative for thromboprophylaxis in MM since they do not require monitoring and spare patents from daily injection [48].…”

Cardiac Care of Patients with Cardiac Amyloidosis

“…According to the consensus statement from the International Myeloma Working Group, patients receiving immunomodulatory drugs should be administered appropriate thromboprophylaxis (either antiplatelet or anticoagulation pharmacotherapy) based on their individual risk factors for the first 4 to 6 months of treatment [74]. In a recent phase 2 pilot study the non-vitamin K oral anticoagulant apixaban was used for thromboprophylaxis in multiple myeloma patients who were receiving immunomodulatory drugs with promising results [75]. Practically, thromboprophylaxis in often maintained while the risk for thromboembolism remains high, and as long as it is tolerated by the patient, avoiding bleeding complications.…”