Low Venous Thromboembolic Risk With Bortezomib in Multiple Myeloma and Potential Protective Effect With Thalidomide/Lenalidomide-based Therapy: Review of Data From Phase 3 Trials and Studies of Novel Combination Regimens

Abstract

Patients with multiple myeloma (MM) are at elevated risk of venous thromboembolism (VTE), specifically deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE risk in MM is increased by various patient- and disease-related factors. The type of anti-MM therapy represents a key factor, with a substantially elevated VTE risk in patients treated with the immunomodulatory drugs (IMiDs) thalidomide or lenalidomide in combination with dexamethasone and/or chemotherapy; VTE risk with lenalidomide-dexamethasone is further increased with concomitant erythropoietin. By contrast, treatment with the proteasome inhibitor bortezomib, alone or in combination, does not increase VTE risk; rates of DVT/PE do not appear affected by the use of erythropoiesis-stimulating agents. Bortezomib has shown antihemostatic effects in patients with relapsed or refractory MM, which supports that it exerts antithrombotic actions and thus potentially provides a protective effect in combination with regimens with an elevated VTE risk. Herein, we review data from phase 3 trials of bortezomib- and/or IMiD-based therapy in frontline MM, together with other studies of novel combination regimens. Despite the confounding effect of variable VTE prophylaxis, bortezomib-based regimens were typically associated with DVT/PE rates of ≤5%, similar to those seen with melphalan-prednisone and dexamethasone, whereas IMiD-based bortezomib-free regimens were generally associated with higher rates. Direct comparisons of regimens of thrombogenic potential with or without bortezomib demonstrated lower VTE risk with bortezomib. Between-study comparisons of VTE risk support these findings. Taken together, these data confirm the low VTE risk associated with bortezomib and support a potential protective effect of bortezomib in combination with IMiD-based regimens associated with elevated VTE risk.