Effects of Multiple Myeloma (MM) Therapy and Type of Thromboprophylaxis On the Incidence and Timing of Venous Thromboembolism (VTE) and Factors Predictive of VTE.

Patients (pts) with MM are at increased risk for VTE due to various risk factors related to the host, disease, and treatment. Immunomodulatory drugs (IMiDs) such as thalidomide and lenalidomide have further increased the risk of VTE. Several studies have shown the VTE risk can be reduced with the use of low molecular weight heparin (LMWH) or aspirin thromboprophylaxis. Based on these findings, VTE thromboprophylaxis has been recommended in pts receiving IMiDs + Dexamethasone (Dex), but the impact of these guidelines on patient outcomes in clinical practice is unclear. The objective of this observational study was to evaluate the incidence, timing and risk factors of VTE and the impact of different types of thromboprophylaxis on the incidence of VTE.

This was a retrospective cohort study, and included all MM pts newly referred to the M.D. Anderson Cancer Center in 2006. Medical records of these pts were reviewed for the type and site of VTE, the incidence and timing of VTE during the five-year period from the referral date, and the risk factors, including pt demographics, co-morbidities, baseline laboratory values, types of MM and treatment, and types of thromboprophylaxis. Univariate and multivariate proportional hazard models were fitted to find the independent risk factors predictive of VTE. The stepwise selection method was employed to build a multivariate model using variables with p<0.15 in univariate analysis.

The cumulative incidence of VTE was 24% (38/159 pts) during the 5-year follow up period. Of the 38 pts with VTE, 25 (66%) had deep vein thrombosis (DVT), 11 (29%) had pulmonary embolus (PE), and 2 had concurrent DVT and PE. Most of the pts (32/38, 84%) had VTE within 1 year from the referral date. The incidence of recurrent VTE among these pts was 27.5% (11/38 pts), for a total of 52 episodes. Since the majority of VTEs and recurrences were within one year, we examined the risk factors for VTE during this period. Treatment with IMiDs + Dex and thromboprophylaxis with LMWH or Coumadin were independent predictive factors as shown below.

The incidence of VTE was highest in pts exposed to IMiDs + Dex (30/38 pts), even after discontinuation of treatment, with most episodes (17/30) occurring during the preparation (7/30) or within 30 days (10/30) following hematopoietic stem cell transplantation (HSCT), when most (16/17) pts were not receiving anti-coagulants.

These findings suggest that patients treated with IMiDs + Dex are at high risk for VTE, even after discontinuation of this treatment, especially, during and after the HSCT period. Future studies are needed to investigate VTE prevention strategies for this high-risk pt population.

No relevant conflicts of interest to declare.