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

Abstract

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 ¼ .001), although only significant for upper extremity DVT (P ¼ .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 ¼ .158). Logistic regression analysis identified thalidomide therapy (P ¼ .001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418-4.159) and prophylactic EPO (P ¼ .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.

Thrombosis in multiple myeloma (MM)

“…23 Furthermore, the use of anthracyclins and erythropoietin has also been associated with a higher incidence of VTE. 24,25 …”

Thrombin generation in newly diagnosed multiple myeloma during the first three cycles of treatment: An observational cohort study

“…Among hematologic malignancies, multiple myeloma (MM) is associated with the highest risk of thrombosis, particularly during the first months of first‐line treatment, and VTE event is associated with a lower survival rate in this setting . Immunomodulatory drugs (IMiDs) are known to be associated with an increased VTE risk, but the mechanism underlying this phenomenon is poorly understood . Current guidelines propose aspirin or low‐molecular‐weight heparin (LMWH) for thromboprophylaxis in MM patients treated with IMiDs, based on VTE risk stratification.…”

A model of hematopoietic stem cell proliferation under the influence of a chemotherapeutic agent in combination with a hematopoietic inducing agent

“…However, one has to balance the cost of these treatments with respect to clinical benefit. Equally relevant is the risk of inducing adverse side effects through the use of HIAs such as venous thromboembolism and tumor progression [28,29]. In future work, we will attempt to capture the pharmacokinetic pattern and fluctuations of different drug effects with respect to proliferating stem cells.…”