Evaluation of the Relationship Between Venous Thromboembolism Risk Factors and the Use of Antithrombotic Prophylaxis in Multiple Myeloma Patients Treated with Thalidomide and Dexamethasone Combination Regimens
Authors: Brandenburg Nancy A , Goss Thomas F , Knight Tyler , Xu Xiao , Knight Robert D. 
Published: April 2020

Abstract
Background: The efficacy of the thalidomide and dexamethasone combination regimens (T+D) in the treatment of multiple myeloma (MM) has been documented. Venous thrombotic events (VTE) have been associated with T+D regimens in patients who may also have individual and disease-specific risk factors for VTE. Antithrombotic prophylaxis (AP) strategies based upon risk factors recently have been proposed (Palumbo et al., Leukemia 2007).
Objectives: To assess the relationship between known VTE risk factors on the probability of prescription antithrombotic prophylaxis (AP) in a community-based cohort of MM patients receiving T+D and to evaluate secular trends in prescribing patterns (exclusive of over-the-counter (OTC) aspirin).
Methods: An analysis of MM patients treated with T+D from 2004–2007 was performed using the IHCIS National Managed Care Benchmark Database from Ingenix, Inc. Diagnoses, procedures and medications were evaluated using ICD-9-CM, CPT, HCPCS and NDC codes. VTE risk factors among MM patients were evaluated as were secular trends in the proportion of patients receiving AP regimens (exclusive of OTC aspirin therapy) and the proportion of patients receiving high-dose (cumulative dose ≥480 mg over the initial 28 day cycle) vs. low-dose dexamethasone (cumulative dose ≤ 160 mg). Risk factors present prior to T+D therapy (as identified by Palumbo et al.) included age, congestive heart failure, atrial fibrillation, recent (≤ past 90 days) stroke, other peripheral vascular disease, diabetes, infection, chronic renal disease, recent surgery, recent hospitalization, use of central venous catheter, chemotherapy, and use of erythropoietin-stimulating agents (ESA). Outcomes of interest included secular trends by half-year in the proportion of patients receiving AP regimens in combination with T+D and in the proportion of patients receiving high vs. low dose dexamethasone regimens. Odds ratios (OR) with 95% confidence intervals (CI) were estimated from a multivariate logistic regression model of AP use as a function of identified risk factors with a p-value ≤ 0.10 for retention in the model.
Results: Among 1732 patients first receiving T+D between 2004–2007, 12.4% received prescription AP simultaneously with T+D, and no secular trend in the overall proportion of T+D patients receiving prophylaxis was observed. In 2007, the proportion of all patients starting T+D regimens with low-dose dexamethasone was 35.9% in the first half of the year in contrast to 58.7% in the second half of the year. Among all patients, 66.3% had at least one risk factor. Among patients with at least two risk factors (N=837; 48.3%), 14.7% received prescription AP simultaneously with T+D. Independent predictors of prescription AP use include age (OR=0.98; CI= 0.97, 1.00), stroke (OR=3.06; CI=0.88, 10.66), peripheral vascular disease (OR=2.69; CI=1.47, 4.93), recent surgery (OR=1.93; CI=1.42, 2.62), and concomitant ESA use (OR=1.67; CI=1.19, 2.34).
Conclusions: While the likelihood of thromboprophylaxis is increased in the presence of several well-known risk factors, additional consideration of thromboprophylaxis among patients with recognized VTE risk factors may be clinically warranted. Further reductions in VTE events may be anticipated should recent prescribing patterns of T+D employing low-dose dexamethasone continue.