Thrombotic complications following treatment of multiple myeloma with immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide)
- Jeffrey Zonder, MD
Jeffrey Zonder, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
- Section Editors
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Robert A Kyle, MD
Robert A Kyle, MD
- Section Editor — Plasma Cell Disorders
- Professor of Medicine
- Mayo Medical School
The association between cancer and venous thromboembolic events (VTE) has been well documented. There are several possible mechanisms involved, including acquired abnormalities involving clotting factors and the coagulation cascade, extrinsic vessel compression by tumor masses, immobility, surgery, the presence of indwelling central venous catheters, as well as the simultaneous presence of an inherited hypercoagulable state (eg, factor V Leiden). (See "Risk and prevention of venous thromboembolism in adults with cancer" and "Pathogenesis of the hypercoagulable state associated with malignancy".)
Patients with multiple myeloma (MM) or the precursor lesion monoclonal gammopathy of undetermined significance (MGUS) have an increased incidence of venous thromboembolism (VTE). In addition, a few studies have suggested an increased risk of arterial thromboembolism (ATE) in these populations as manifested by stroke, transient ischemic attack, myocardial infarction, or symptomatic peripheral artery disease. The increased rate of VTE appears to be both a result of the malignancy itself and the therapy given. In particular, the rate of VTE is particularly high for patients with MM treated with combination chemotherapy that contains thalidomide or a thalidomide analog such as lenalidomide.
The thrombotic risk associated with the use of thalidomide and its analogues as treatment for MM will be discussed here. Thrombotic risk following the use of other antineoplastic agents (eg, tamoxifen, L-asparaginase) and issues related to the treatment of VTE are presented separately. (See "Drug-induced thrombosis in patients with malignancy", section on 'L-asparaginase' and "Overview of the treatment, prognosis, and follow-up of acute pulmonary embolism in adults" and "Overview of the treatment of lower extremity deep vein thrombosis (DVT)" and "Drug-induced thrombosis in patients with malignancy", section on 'Tamoxifen'.)
Patients with multiple myeloma are at increased risk of having comorbidities known to be risk factors for the development of venous thromboembolism (VTE) in the general population. In addition, treatment with thalidomide and its analogs has been associated with high rates of VTE. Thalidomide has a wide spectrum of biological effects, including immune modulation, alteration of adhesion molecule and cytokine expression, and inhibition of angiogenesis . (See 'General risk factors' below and "Overview of angiogenesis inhibitors", section on 'Immunomodulatory drugs (IMiDs)'.)
While the exact mechanism by which thalidomide contributes to thrombosis is not known, the following mechanisms have been postulated:
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- POTENTIAL MECHANISMS
- INCIDENCE AND RISK FACTORS
- General risk factors
- Thalidomide-based therapy
- - Single agent thalidomide
- - Thalidomide plus dexamethasone
- - Thalidomide plus melphalan and prednisone
- - Thalidomide plus anthracycline
- Thalidomide analogues
- - Lenalidomide in myeloma
- - Lenalidomide in other cancers
- - Pomalidomide
- VENOUS THROMBOEMBOLISM PROPHYLAXIS
- Choice of agent
- - Risk stratification
- - Lower risk setting
- - Standard risk setting
- - High risk setting
- Low molecular weight heparin
- - Patients at high risk of bleeding
- Length of prophylaxis
- DIAGNOSIS AND MANAGEMENT OF VENOUS THROMBOEMBOLISM
- SUMMARY AND RECOMMENDATIONS