In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
Purpose In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens. Patients and Methods A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment. Results Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, −3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, −1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded. Conclusion In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.
IntroductionOver the last decade, major advances in the treatment of multiple myeloma (MM) have been reported with the use of autologous stem-cell transplantation [1][2][3][4] and, more recently, of novel agents targeting the tumor clone and the bone marrow microenvironment. 5 In this setting, thalidomide represents a new treatment paradigm because of its alternative mechanisms of action that include disruption of myeloma-bone marrow stromal cell interactions, inhibition of cytokine secretion, and immunomodulatory effects. The observation that increased bone marrow angiogenesis correlates with advanced phases of MM, 6 along with the welldocumented in vitro antiangiogenic activity of thalidomide, 7 led to the investigational use of this agent in patients with advanced and refractory MM. 8 Response rates in the 30% range initially reported by Singhal et al 8 were extended and confirmed by other groups (for a review, see Cavenagh and Oakervee 9 and Dimopoulos et al 10 ). Subsequent combination of thalidomide with dexamethasone increased the rate of response up to 50% to 55%, 11,12 suggesting a synergism between these agents and providing the rationale for their use as primary therapy for patients with symptomatic MM. Results of 3 phase-2 studies with thalidomide-dexamethasone (Thal-Dex) in preparation for subsequent autologous transplantation 13-15 and a randomized comparison of Thal-Dex with dexamethasone alone 16 were promising in terms of response rate and collection of adequate quantities of peripheral blood stem cells (PBSCs). Based on these data, Thal-Dex has been proposed, and is currently accepted at many centers, as a front-line treatment option for patients with symptomatic MM, particularly if it is planned to offer subsequent high-dose therapy with autologous transplantation. However, no comparative study of Thal-Dex with vincristinedoxorubicin-dexamethasone (VAD), the reference treatment used so far to reduce tumor cell mass before autologous transplantation, has been reported. To address this issue, we performed a retrospective matched case-control analysis of 200 patients with symptomatic MM who were primarily treated with Thal-Dex (n ϭ 100) or VAD (n ϭ 100) in preparation for autologous stem-cell transplantation as part of 2 consecutive studies conducted from 1996 to 2004. Table 1; the 2 groups were comparable with respect to the major presenting variables known to potentially affect clinical outcome. Both studies were approved by local ethical committees of participating centers. Informed consent was provided according to the Declaration of Helsinki.
Patients, materials, and methods
Patients and criteria of matching
Study design and treatment regimensBy design of both studies, Thal-Dex and VAD were planned to be administered for 4 months in an attempt to reduce tumor cell mass before collection of PBSCs and subsequent autologous transplantation. Details on treatment regimens were given elsewhere. 4,15 Briefly, thalidomide was given orally at the starting dose of 100 mg/d for 14 days and then increa...
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