Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis

BACKGROUND: Venous thromboembolism (VTE) is a significant but poorly understood complication in patients with newly diagnosed multiple myeloma (NDMM). As a result, most patients receive thromboprophylaxis with low molecular weight heparin (LMWH). The purpose of this retrospective study was to identify risk factors for VTE in NDMM and evaluate the effectiveness of LMWH. METHODS: A total of 604 patients with newly diagnosed myeloma completed 3 induction cycles with multiagent chemotherapy with up-front randomization to thalidomide between 1998 and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part of an exercise trial. The primary study endpoint was grades 3-4 VTE. RESULTS: A total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with a higher incidence among EPO recipients (P=.001), although only significant for upper extremity DVT (P=.0002). The EPO-treated patients had higher hemoglobin (Hb) levels throughout the study (P <.0005), although no relationship between higher Hb levels and increasing incidence of VTE could be shown. A history of VTE was a strong predictor of VTE on univariate analysis (P <.000005). Enoxaparin did not reduce the rate of VTE (P=.158). Logistic regression analysis identified thalidomide therapy (P=.001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418-4.159) and prophylactic EPO (P=.002; OR, 2.488; 95% CI, 1.432-4.324) as risk factors for VTE. Myeloma response and survival were not negatively affected by prophylactic EPO or VTE. CONCLUSIONS: Prophylactic EPO, thalidomide therapy, and VTE history, but not higher Hb levels, were found to increase the risk of VTE among NDMM patients receiving multiagent chemotherapy. This risk was not found to be reduced in this population by LMWH thromboprophylaxis. Cancer 2012; 118: 549-57. (C) 2011 American Cancer Society.