Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma

Abstract

The incidence of venous thromboembolism (VTE) is more than 1 per thousand annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients with < or = 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis.

Venous thromboembolism in hematopoietic stem cell transplant recipients

“…The International Myeloma Working group and ASCO recommend prophylaxis with either aspirin or LMWH for lower risk patients, and LMWH for higher risk patients receiving thalidomide or lenalidomide. 47,61 Hospitalized patients Based on randomized clinical trials of thromboprophylaxis in medically ill hospitalized patients, 62,63 and a meta-analysis that demonstrated 40% lower rates of VTE with pharmacologic prophylaxis versus placebo, 64 the current ACCP 52 and ASCO guidelines 47 strongly recommend thromboprophylaxis in hospitalized medically ill and cancer patients, respectively. However, trials of thromboprophylaxis did not include HSCT patients who are not specifically included in these recommendations.…”

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

“…All patients treated with Rd require antithrombosis prophylaxis. Aspirin is adequate for most patients, but in patients who are at higher risk of thrombosis, either low-molecular weight heparin or coumadin is needed [53][54][55].…”

Treatment of multiple myeloma and arterial thrombosis

“…Taking all this into account, one should consider preventive measures to reduce thrombotic complications in multiple myeloma patients receiving chemotherapy, especially when combined with thalidomide. Currently, there are only recommendations on thromboprophylaxis for multiple myeloma patients who are treated with thalidomide-or lenalidomide-containing regimens [10]. In these patients, thromboprophylaxis with low molecular weight heparin (LMWH) is effective in reducing thrombotic complications [9].…”

“…In these patients, thromboprophylaxis with low molecular weight heparin (LMWH) is effective in reducing thrombotic complications [9]. Several studies have shown that aspirin is also effective in reducing thrombotic events [10]. In a recent prospective, multicenter study, low-dose warfarin, LMWH and aspirin were compared in patients treated for newly diagnosed multiple myeloma.…”