Venous thromboembolism (VTE) is highly prevalent in Multiple Myeloma (MM) patients, however a reliable VTE prediction tool in MM remains under study. The IMPEDE VTE score has recently emerged as a novel risk prediction tool for VTE in MM but needs external validation in different cohorts. We conducted a retrospective cohort study to validate this score. We reviewed 839 patients who were newly diagnosed with MM between 2010 and 2015 at Cleveland Clinic and included 575 patients in final analysis. The 6-month cumulative incidence of VTE among all patients was 10.7% (95% CI: 8.2 – 13.2) and the c-statistic of the IMPEDE VTE score to predict VTE within 6 months of treatment start was 0.68 (95% CI: 0.61 – 0.75). The 6-month cumulative incidence of VTE was 5.0% (95% CI: 2.1 – 7.9) in the low risk group, compared to 12.6% (95% CI: 8.9% – 16.4%) and 24.1% (95% CI: 12.2 – 36.1) in the intermediate and high risk groups (p<0.001 for both). In addition, a higher proportion of patients in the VTE cohort had ECOG performance status of ≥2 as compared to the no VTE cohort (33% vs. 16%, p=0.001). Other MM characteristics such as stage, immunoglobulin subtype, and cytogenetics were not found to be predictors of VTE. In summary, we have validated the IMPEDE VTE score in our patient cohort and our findings suggest that it can be utilized as a VTE risk stratification tool in prospective studies looking into investigating VTE prophylaxis strategies in MM patients.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients. Multiple Myeloma (MM) is the second most common hematological malignancy and associated with 9-fold increased risk of VTE compared to the general population . The higher risk of VTE in MM patients is multifactorial and related to patient- , MM- and treatment-related factors . The monoclonal protein can lead to hyperviscosity in 2% to 6% of MM patients, interfere with fibrin clot formation 7 85 , and act as a procoagulant antibody. Elevated cytokine levels in MM patients such as interleukin-6, tumor necrosis factor alpha, and vascular endothelial growth factor further enhance the thrombosis risk. Immobility due to increased incidence of bone fractures, use of central venous catheter, and erythropoiesis-stimulating agents are additional risk factors for VTE in MM. Several commonly used plasma cell directed drugs, 90 such as dexamethasone, immunomodulatory drugs (IMiD), alkylating agents, and doxorubicin, alter hemostatic pathways and thus promote thrombogenesis. A majority of VTE events in MM patients occur within 6 months of treatment initiation. In 2008, the 94 International Myeloma Working Group (IMWG) recommended different VTE prophylaxis strategies based 95 on a number of VTE risk factors; aspirin and low molecular weight heparin/warfarin were offered for patients with ≤1 and ≥2 risk factors, respectively. These recommendations were based on consensus opinion and limited evidence. Despite the implementation of those guidelines in the Myeloma XI trial, a phase III 98 multicenter randomized clinical trial which included 4358 newly diagnosed MM patients, the cumulative incidence of VTE within 6 months of induction therapy was more than 10% in all study arms. Importantly, 100 only 55% of patients who had thrombotic events in this trial were in the high-risk group for VTE based on the IMWG criteria. Sanfilippo et al. have recently developed the IMPEDE VTE score, a risk prediction 102 tool for VTE in MM, using 4446 patients within the veterans administration central cancer registry and 103 validated this using 4256 patients in the Surveillance, Epidemiology, End Results (SEER)-Medicare database. Patients were stratified into three different risk groups based on the IMPEDE VTE score and 105 the 6-month cumulative incidence of VTE were 15.2%, 8.3%, and 3.3% among patients in the high-risk, intermediate-risk, and low-risk groups at the time of induction, respectively. Therefore, the IMPEDE VTE score may provide a better risk stratification for VTE in newly diagnosed MM 109 patients compared to current risk stratification strategies. Herein, we validated the IMPEDE VTE score in 110 our patient cohort.

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Journal of Clinical Trials

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