VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.

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.

Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatmentrelated side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomibthalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials MP. 11,12 In patients aged 75 years or over, the efficacy of VMP was less evident: the 3-year OS was shorter in comparison with patients aged under 75 years (55% vs. 74%). The incidence of any grade 3-4 AEs was 91% and bortezomib discontinuation rate due to AEs was 34%. Both VMP and MPT are now considered the new standards of care for newly diagnosed MM patients aged 65 years or over. Recently, the combination of bortezomib and thalidomide with or without alkylating agents has shown to be highly effective. 13,14 The weekly administration of bortezomib reduced the incidence of AEs, especially peripheral neuropathy and gastrointestinal toxicity, without affecting efficacy.13,14 Nevertheless, outcome was mainly improved for patients aged under 75 years, while limited advantage was reported in patients aged 75 years or over.14 These data lead to the question as to whether less toxicity may translate into more efficacy, especially in unfit elderly patients.In this meta-analysis of individual patient data from 4 randomized trials, we assessed the influence of age, organ damage, development of treatment-related AEs and drug discontinuation as predictive factors of outcome in elderly newly diagnosed MM patients receiving MP, MPT, VMP, or bortezomib and thalidomide combination (bortezomib, thalidomide and prednisone [VTP] or bortezomib, melphalan, prednisone and thalidomide [VMPT]). Design and Methods Study design and treatmentsPa...

Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

Patients in complete clinical remission after myeloablative allogeneic stem cell transplantation (allo-SCT) were enrolled in a longitudinal study to assess the predictive value of molecular monitoring. Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to generate a clonespecific molecular marker in 48 of 70 patients. Of these 48 patients, 16 (33%) attained durable PCR-negativity after transplantation, whereas 13 (27%) remained persistently PCR-positive and 19 (40%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCRmixed patients, and 100% for PCR-positive patients. Within the group studied it was not possible to identify any clinical feature predictive of durable PCR-negativity. We believe that these findings could prompt the design of prospective studies to evaluate if the treatment of molecular disease can extend remission duration and survival.