Venous Thromboembolic Prophylaxis Following Treatment Initiation for Multiple Myeloma
Authors: Calip Gregory Sampang , Zhou Jifang , Sweiss Karen , Patel Pritesh , Asfaw Alemseged Ayele , Lee Todd , Chiu Brian C.-H. , Nutescu Edith A. 
Published: October 2019

Abstract
INTRODUCTION: Multiple myeloma (MM) induces a hypercoagulable state with increased risk of venous thromboembolism (VTE) due to higher blood viscosity, circulating immunoglobin, inflammatory cytokines, procoagulant monoclonal protein and cytotoxic therapies. Thromboprophylaxis is typically indicated for immunomodulator-based treatment or if a patient has multiple VTE risk factors, though evidence on the patterns and effectiveness of antithrombotic medications in this setting is lacking. Our objective was to describe VTE prophylaxis interventions in patients with MM in a large commercially-insured U.S. population.
METHODS: We performed a retrospective cohort study of patients with incident MM initiating first-line treatment between 2009 and 2015 using medical and pharmacy administrative claims data from the Truven Health MarketScan Research Database. Patients were required to have continuous enrollment for at least 12 months prior to MM diagnosis and 6 months following treatment initiation (unless died). Information on MM treatments including immunomodulatory drugs (IMiDs: thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (PIs: bortezomib) and other oral and intravenous chemotherapy agents was collected. Baseline characteristics related to risk of VTE were documented, including medical conditions, procedure-related risk factors, other medications associated with increased VTE risk and MM-treatment related risk factors defined by the International Myeloma Working Group. Medications used for VTE prophylaxis following MM treatment initiation (and prior to the occurrence of a subsequent VTE event) included antiplatelet agents, low molecular weight heparin (LMWH), warfarin and direct oral anticoagulants (DOAC). We used multivariable logistic and polytomous regression models to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) associated with receipt of VTE prophylaxis and specific antithrombotic medications used respectively.
RESULTS: Among 7405 MM patients, the mean age was 64.9 years (standard deviation: 11.6), 43% were female, and more than half of patients received IMiD-based treatment (52%). Overall, 20% of patients in the cohort received VTE prophylaxis with any agent [antiplatelet agent (5%), LMWH (6%), warfarin (7%) and DOAC (2%)]. Patients treated with IMiDs had fewer VTE risk factors at baseline compared with MM patients receiving non-IMiD based treatment (2 or more risk factors: 24% vs. 38%, p<0.01); however, a higher proportion of patients receiving IMiDs received VTE prophylaxis with any agent (25% vs. 14%, p<0.01). The median number of days receiving VTE prophylaxis was between 92 and 109 days for antiplatelet, warfarin and DOAC therapies and 23 days for LMWH. Having 2 or more VTE risk factors at baseline was associated with higher odds of receiving VTE prophylaxis (OR 1.58, 95% CI 1.40-1.79). MM treatments associated with receipt of any VTE prophylaxis included thalidomide (OR 3.17, 95% CI 2.51-4.00), lenalidomide (OR 2.14, 95% CI 1.87-2.46) and doxorubicin-including chemotherapy (OR 3.48, 95% CI 2.36-5.13) but not pomalidomide (OR 0.97, 95% CI 0.55-1.70) or bortezomib (OR 0.91, 95% CI 0.79-1.05). VTE prophylaxis with antiplatelet agents was associated with history of atrial fibrillation (OR 2.01, 95% CI 1.50-2.70) and recent central venous catheter use (OR 1.58, 95% CI 1.25-2.00); whereas prophylaxis with LMWH, warfarin or DOAC was associated with history of a VTE event in the prior 12 months (OR 3.59, 95% CI 2.74-4.69), chronic kidney disease (OR 4.48, 95% CI 3.67-5.47), recent hip fracture (OR 1.68, 95% CI 1.12-2.52) and recent hospitalization (OR 1.27, 95% CI 1.08-1.49).
CONCLUSIONS: VTE prophylaxis is generally recommended with the presence of 2 or more VTE risk factors or when initiating IMiD therapy in patients with multiple myeloma. In our cohort, half of newly diagnosed MM patients initiated IMiD-based first-line therapy; of which; one in four IMiD initiators also received prophylaxis with antithrombotic or anticoagulant medications. Comprehensive evidence on the comparative effectiveness of VTE prophylaxis strategies in multiple myeloma is needed to guide prevention of this serious adverse outcome.

Disclosures
Patel: Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria.