Thromboembolic Events (TEE) with Lenalidomide-Based Therapies for Multiple Myeloma (MM): Emory Experience.

Lenalidomide is a derivative of thalidomide with an additional amino group at position 4 and removal of a carbonyl group that has enhanced efficacy and reduced toxicity relative to its parent compound. However, studies have reported the incidence of TEE from 3-23.8%. We proceeded to evaluate incidence and risk factors of TEE associated with lenalidomide-based therapies in patients with multiple myeloma at our institution.

We reviewed 152 records of patients that were prescribed lenalidomide from prescribing information obtained from Celgene pharmaceuticals as well as reviewing patient information from all clinical trials from 2004 until October 2008. IRB approval was obtained. 146 patients (pts) were included in study after excluding 6 pts in whom lenalidomide was used for non-myeloma indications. Lenalidomide was indicated for induction in 22 (15%) pts and for maintenance/salvage in 124 (85%) pts.

81 (55.5%) pts were male and 65 (44.5%) were female. White pts (65%) contributed to majority of our pt population. Median age (range) is 62 months (23-87); stage III disease is seen in 23 pts (22%); median (range) β-2 microglobulin is 2.68 (0.8-43.51) and median (range) creatinine is 1.05 (0.6-21). Pts received a median (range) of 7 (1-58) cycles. Overall ten (6.8%) TEEs were observed including nine venous TEEs (6.12%) and one arterial TEE (0.68%). Nine pts developed TEE despite being on ASA prophylaxis. Median (range) time to event was 17 weeks (4-158). Median (range) cycles of lenalidomide before the event were 3.5 (1-38). 60% of events took place in the first 4 months of initiation of therapy. On univariate analysis, erythropoietin use vs. none (21.4% vs. 5.3% p=0.023); median number of cycles ≥7 vs. <7 (11.1% vs. 2.7% p=0.044) and previous history of DVT vs. none (20% vs. 4.1%; p=0.014) were identified as significant risk factors. Steroid doses, BMI were not identified as risk factors. On multivariate analysis, age <60 (HR 0.11 95%CI 0.00-0.50; p = 0.021) had a significant protective impact on developing TEE. Median survival (range) in pts with TEE is 102 months (100.4-103.6) and pts without TEE is 99 months (79.38-118.62); log rank 0.125.

Neither high dose steroids nor the BMI were identified as risk factors for TEE. All pts with venous TEE had high risk factors validating the risk model of IMWG. No impact on overall survival was seen between pts with TEE and pts without TEE.

Kaufman:Celgene: Consultancy, Research Funding; Millenium: Consultancy; Genzyme: Consultancy; Merck: Research Funding. Heffner:Millenium: Honoraria. Gleason:Millenium: Consultancy. Lonial:Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.