Incidence and prophylaxis of venous thromboembolic events in multiple myeloma patients receiving immunomodulatory therapy

The diagnosis of multiple myeloma (MM) has been associated to an increased risk of venous thromboembolic events (VTE). Described risk factors that are not exclusive to MM include old age, chemotherapy, immobility, high levels of vascular endothelial growth factor, cancer procoagulant and paraproteinemia. Disease-specific risk factors unique to MM are production of procoagulant autoantibodies, a high incidence of acquired activated protein C resistance, increased levels of factor VIII and von Willebrand factor, and increased production of inflammatory cytokines, mainly IL-6, TNF and C-reactive protein. Treatment regimens that include thalidomide or related compounds such as lenalidomide combined with glucocorticoids and/or cytotoxic chemotherapy were associated with an increased risk of VTE. The risk appears to be particularly high when these immunomodulatory agents are combined with anthracyclines as treatment of newly-diagnosed disease. Combinations including thalidomide plus dexamethasone and/or alkylating agents are associated with an intermediate risk. The same regimens for relapsed/refractory myeloma seem to be associated with a lower risk. The use of newer immunomodulators such as brotezomib seem to reduce the thrombogenic potential. Several different thromboprophylaxis strategies have been effective in lowering the risk of VTE but the data are disputable. None of these VTE prevention strategies have been prospectively compared head-to-head.