Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients.

Cancer patients have an increased risk of venous thrombosis (VT). The association of factor V Leiden (FVL) and the prothrombin 20210A variant with VT in cancer patients is not established. We genotyped 101 cancer patients with VT and 101 cancer patients without VT for these polymorphisms. Five cases and three controls were heterozygous for FVL, yielding an odds ratio of 1.7 (95% confidence interval (CI) 0.3-10.7). Five cases and no controls were heterozygous for prothrombin 20210A, for an odds ratio of 6.7 (95% CI 0.9-infinity). Prothrombin 20210A may be associated with VT risk among cancer patients.

D-dimer as a risk factor for deep vein thrombosis: the Leiden Thrombophilia Study.

We studied the association of D-dimer with the risk of deep vein thrombosis (DVT). D-dimer was measured in 474 patients more than 6 months after diagnosis of a first DVT and in 474 age- and sex-matched controls. For D-dimer above the 70th percentile (130.5 ng/ml), the odds ratio (OR) for DVT was 2.2 (95% CI, 1.6-2.9). The association was unchanged with adjustment for other risk factors. Excluding participants with Factor V Leiden, prothrombin 20210A, or factors VIIIc or IX above the 90th percentile, the OR was 1.6 (95% CI, 1.1-2.3). The risks of DVT with the joint presence of high D-dimer and either factor V Leiden or prothrombin 20210A were increased 12.4-fold (95% CI 5.6-27.7) and 7.2-fold (95% CI 2.1-25.1), respectively. Higher D-dimer concentration was associated with the risk of DVT, and was supra-additive to the risks associated with factor V Leiden and the prothrombin 20210A variant. Persistence of this association in the absence of other hemostatic risk factors for DVT suggests that high D-dimer may be related to other, as yet unknown, risk factors for venous thrombosis. Confirmation of these findings is desirable.