In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progressionfree survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-totreat analysis; VTD, n ‫؍‬ 236; TD, n ‫؍‬ 238). This per-protocol analysis (VTD, n ‫؍‬ 160; TD, n ‫؍‬ 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTDtreated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the

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High-dose (200 mg/m 2 , MEL200) and intermediate-dose melphalan (100 mg/ m 2 , MEL100) showed significant activity in myeloma. In a phase 3 study, 298 patients were randomly assigned to receive 2 autologous transplantations after conditioning with MEL200 or MEL100. Ninetysix of 149 (64%) completed MEL200 and 103 of 149 (69%) MEL100. Best response to MEL200 was: complete remission 22 of 149 (15%); partial remission 95 of 149 (64%), for an overall response rate of 79%. Best response to MEL100 was: complete remission 12 of 149 (8%); partial remission 95 of 149 (64%), for an overall response rate of 72%. Overall survival did not differ (P ‫؍‬ .13); median progression-free survival (31.4 vs 26.2 months, P ‫؍‬ .01), median time to progression (34.4 vs 27.0 months, P ‫؍‬ .014) were longer in the MEL200. Treatment-related mortality was 3.1% in the MEL200 and 2.9% in the MEL100 group. Severe neutropenia and infections were marginally superior, whereas severe thrombocytopenia, mucositis, gastrointestinal adverse events, and the overall occurrence of at least 1 nonhematologic grade 3 or 4 adverse event were significantly higher in the MEL200 cohort. We conclude that MEL200 leads to longer remission duration and should be considered the standard conditioning regimen for autologous transplantation. This study was registered at www.clinicaltrials.gov as #NCT00950768. IntroductionSeveral studies support the benefit of high-dose melphalan with stem cell rescue in patients with newly diagnosed multiple myeloma. [1][2][3] Results from randomized trials are in favor of tandem autologous transplantation rather than only 1 procedure, even though a real benefit remains to be determined. 4,5 Most conditioning regimens have been based on either melphalan alone or in combination with other agents. Melphalan at 200 mg/m 2 (MEL200) is considered the standard dose for conditioning patients younger than 65 years. 6 Older age and comorbidities may become limiting factors. In a retrospective case-matched study, 90 newly diagnosed patients treated with 2 courses of melphalan at 100 mg/m 2 (MEL100) were compared with a control group of 90 pair mates, matched for serum ␤-microglobulin levels and Durie-Salmon clinical stage, and treated up-front with 2 MEL200 courses. 7 Median progression-free survival (PFS) was significantly superior in the MEL200 group, but overall survival (OS) was not different. Moreover, hematologic and nonhematologic toxicities were significantly reduced in the MEL100 group. Here, we report a phase 3 clinical trial comparing 2 doses of melphalan, MEL200 versus MEL100, in newly diagnosed multiple myeloma. The underlying hypothesis was that rather than give 2 very intensive preparative regimens before autologous stem cell infusions, providing effective myeloma cell kill, a less toxic reducedintensity conditioning would be better tolerated, especially in older patients, and equally effective. Methods PatientsFrom October 2001 to July 2006, 298 newly diagnosed myeloma patients younger than 65 years were enrolled in a prospecti...

Allogeneic stem cell transplantation (allo-SCT) using reduced-intensity conditioning (RIC) is a feasible procedure in selected patients with relapsed multiple myeloma (MM), but its efficacy remains a matter of debate. The mortality and morbidity related to the procedure and the rather high relapse risk make the use of allo-SCT controversial. In addition, the availability of novel antimyeloma treatments, such as bortezomib and immunomodulatory agents, have made allo-SCT less appealing to clinicians. We investigated the role of RIC allo-SCT in patients with MM who relapsed after autologous stem cell transplantation and were then treated with a salvage therapy based on novel agents. This study was structured similarly to an intention-to-treat analysis and included only those patients who underwent HLA typing immediately after the relapse. Patients with a donor (donor group) and those without a suitable donor (no-donor group) were compared. A total of 169 consecutive patients were evaluated retrospectively in a multicenter study. Of these, 75 patients found a donor and 68 (91%) underwent RIC allo-SCT, including 24 from an HLA-identical sibling (35%) and 44 from an unrelated donor (65%). Seven patients with a donor did not undergo allo-SCT for progressive disease or concomitant severe comorbidities. The 2-year cumulative incidence of nonrelapse mortality was 22% in the donor group and 1% in the no-donor group (P < .0001). The 2-year progression-free survival (PFS) was 42% in the donor group and 18% in the no-donor group (P < .0001). The 2-year overall survival (OS) was 54% in the donor group and 53% in the no-donor group (P = .329). In multivariate analysis, lack of a donor was a significant unfavorable factor for PFS, but not for OS. Lack of chemosensitivity after salvage treatment and high-risk karyotype at diagnosis significantly shortened OS. In patients who underwent allo-SCT, the development of chronic graft-versus-host disease had a significant protective effect on OS. This study provides evidence for a significant PFS benefit of salvage treatment with novel drugs followed by RIC allo-SCT in patients with relapsed MM who have a suitable donor.

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