Risk Factors for Venous Thromboembolism and the Use of Antithrombotic Prophylaxis in Multiple Myeloma Patients Treated with Lenalidomide and Dexamethasone Combination Regimens.

Lenalidomide and dexamethasone combination therapy (LEN/DEX) is efficacious in the treatment of multiple myeloma (MM). Venous thrombotic events (VTE) have been associated with LEN/DEX regimens in patients who may also have individual and disease-specific risk factors for VTE (Palumbo et al., Leukemia 2008). Fewer VTE events have been reported among patients receiving low-dose corticosteroids (Menon et al., 2008; Jacobus et al., 2008). Antithrombotic prophylaxis (AP) strategies based on risk factors have been proposed.

To assess the relationship between known VTE risk factors and the probability of prescription AP in a community-based cohort of MM patients receiving concomitant LEN/DEX therapy and to evaluate secular trends in prescribing patterns (exclusive of over-the-counter [OTC] aspirin).

An analysis of MM patients treated with LEN/DEX from January 1, 2006 – April 30, 2008 (1H2008) was performed using the Integrated Healthcare Information Services (IHCIS) National Managed Care Benchmark Database from Ingenix, Inc. Diagnoses, procedures, and prescription medications were evaluated using ICD-9-CM, CPT, HCPCS, and NDC codes (IHCIS does not capture OTC drugs). VTE risk factors among MM patients were evaluated. The proportion of patients receiving AP regimens and the proportion of patients receiving high- (cumulative dose ≥ 480 mg over the initial 28 day cycle) or medium-dose (cumulative dose ≤ 480 mg, but > 160 mg) dexamethasone vs. low-dose dexamethasone (cumulative dose ≤ 160 mg) were also evaluated. AP prophylaxis was assessed during the first 120 days of LEN/DEX therapy or prior to VTE event in patients who experienced VTE within the first 120 days of therapy. Risk factors present prior to the initial LEN/DEX prescription included age, gender, previous VTE, other peripheral vascular disease, congestive heart failure, atrial fibrillation, diabetes, chronic renal disease, respiratory failure, use of central venous catheter, recent (≤ past 90 days) stroke, recent infection, recent surgery, recent hospitalization, recent chemotherapy, recent use of erythropoietin-stimulating agents and number of risk factors (>2 vs. 0-2). Outcomes of interest included secular trends by half-year in the proportion of patients receiving AP regimens in combination with LEN/DEX and in the proportion of patients receiving high/medium 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 selection into the model.

Among 570 patients receiving LEN/DEX between 2006 – 1H2008, 14.0% received prescription AP. Among patients receiving high/medium DEX, 16.3% received AP; among patients receiving low DEX 12.2% received AP. No secular trend in the overall proportion of LEN/DEX patients receiving prophylaxis was observed. Nearly half (47.7%) of the patients had >2 risk factors; among these higher risk patients, 20% received prescription AP. For the half years 1H2007, 2H2007, and 1H2008, the proportion of all patients starting LEN/DEX regimens with low-dose dexamethasone increased from 55.6% to 76.3% to 81.5%, respectively.

Independent positive predictors of prescription AP use include prior chemotherapy (OR=2.71; CI=1.49, 4.90), recent infection (OR=2.16; CI=0.88, 5.32), renal failure (OR=1.72; CI=0.97, 3.05), high/medium dexamethasone dose (OR=1.64; CI=0.98, 2.75), and >2 risk factors (OR=1.63; CI=0.89, 2.99). Patients with respiratory failure (OR=0.23; CI 0.05, 1.01) were less likely to receive AP therapy.

The likelihood of prescription AP is increased by the presence and the number of several VTE risk factors. Recent prescribing trends favoring the use of low-dose dexamethasone among community MM patients may enhance the risk-benefit ratio of LEN/DEX therapy through reduction in VTE events.

Brandenburg: Celgene Corporation: Employment, Equity Ownership. Knight: Covance, Inc: Employment, Equity Ownership; Celgene Corporation: Consultancy. Vassilev: Covance, Inc: Employment, Equity Ownership; Celgene Corporation: Consultancy. Knight: Celgene Corporation: Employment.