Thromboembolism with Immunomodulatory Agents in the Treatment of Multiple Myeloma

Anurag      Singh; Ajeet      Gajra

Abstract

Immunomodulatory agents which include thalidomide and its analogue lenalidomide have recently emerged as an effective treatment option for patients with multiple myeloma. The anti-tumor property of these molecules is probably related to action on tumor microenvironment, anti-angioenesis and several other hitherto less understood mechanisms. Despite promising efficacy, their progress has been complicated by reports of venous thromboembolism in patients receiving these agents. The background rate of thromboembolism is 4-11% in patients with multiple myeloma, which increases to 15-20% in patients who received intensive treatment with thalidomide. The exact mechanism of this phenomenon is not clear but possible explanations include up-regulation of pro-coagulant factors and selective endothelial damage. The development of thromboembolism is also influenced by disease state, performance status, type of chemotherapy and supportive therapy. Multiple treatment strategies for prevention of thromboembolic events in these patients have been proposed including aspirin, heparins and warfarin but there have been no prospective controlled trials comparing the superiority of one prophylactic measure over another. The diagnosis and treatment of thromboses in these patients involves standard guidelines but the optimal duration is not certain. This review discusses incidence, pathogenesis and management of thrombotic events with the use of immunomodulatory agents in the setting of multiple myeloma as well as recent recommendations regarding appropriate prophylaxis and preventive measures.

Keywords: Multiple myeloma, immunomodulatory agents, thalidomide, lenalidomide, thromboembolism, anti-tumor property, anti-angioenesis, pro-coagulant factors, aspirin, heparins, warfarin, venous thromboembolism, hematological neoplasm, thromboprophylaxis, dexamethasone, chemotherapy, monoclonal immunoglobulin, autoantibodies, lupus anticoagulant, interleukin-6, pro-inflammatory cytokines, tumor necrosis factor, CC-4047, doxorubicin-mediated endothelial cell injury, single-agent thalidomide, Refractory Multiple Myeloma, anthracyclines, alkylating agents, etoposide, cisplatin, anticoagulation, vincristine, factor Xa, Cardiac disease