Incidence of venous thromboembolic events (VTE) in multiple myeloma patients receiving lenalidomide (LEN) with and without dexamethasone (DEX).

Abstract

e18559 Background: LEN showed significant efficacy and was generally well tolerated when combined with DEX in two randomized, double-blind, pivotal phase 3 registration trials in relapsed or refractory multiple myeloma (MM). VTEs have been associated with LEN and DEX combination (LEN+DEX) regimens in patients (pts) who may have other risk factors for VTE. Fewer VTEs have been reported among pts receiving low dose DEX. This study examined the incidence of first VTE and associated risk factors among MM pts receiving LEN and LEN+DEX. Methods: An exploratory, retrospective, claims-based study of pts diagnosed with MM and receiving LEN from Jan 2006 – June 2008 was performed using OptumInsight’s Invision Data Mart Multiplan database. Pts receiving additional MM chemotherapies were excluded. DEX dose level was defined over the first four 28-day cycles of LEN as: low (≤160 mg), medium (>160 mg to <480 mg), or high (≥ 480 mg). Cumulative incidence of first VTE (deep vein thrombosis or pulmonary embolism) within 120 days of initiating LEN treatment was calculated from Kaplan-Meier curves. Risk factors for VTE were examined using hazard ratios (HRs) from a Cox model that included demographics, prior MM therapy, comorbid conditions, DEX dose, and prophylactic use of anti-thrombotics. Results: 643 LEN-treated MM pts were identified (mean age 60 years, 60% male, 13.5% with prior VTE). Cumulative incidence of first VTE at 120 days from first LEN dose was 6.1% overall (95% CI 4.4-8.3%) and 7.2% (5.1-10.2%) in LEN+DEX. VTE risk for LEN without DEX (n=190; 66 with other steroids) was 3.4% (1.5-7.5%). VTE risk by DEX dose level was 5.9% (3.6-9.7%) for low DEX (n=286), 7.5% (3.6-15.1%) for medium DEX (n=99), and 12.3% (6.3-23.1%) for high DEX (n=66). Significant risk factors for VTE were prior VTE (HR=3.9; p<0.001), recent surgery (HR=2.1; p=0.047), renal failure (HR=2.2; p=0.023), and high dose DEX (HR=2.3; p=0.045). Conclusions: Incommunity-based MM pts treated with LEN+DEX, VTE risk increases with the dose of DEX. The exact mechanism by which DEX intensity impacts VTE is not clear. In addition to high dose DEX, other known VTE risk factors were observed.