Superiority of the triple combination of bortezomib-thalidomide- dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: The MMVAR/IFM 2005-04 randomized phase III trial from the chronic leukemia working party of the European Group for blood and marrow transplantation

Laurent Garderet, Simona Iacobelli, Philippe Moreau, Mamoun Dib, Ingrid Lafon, Dietger Niederwieser, Tamas Masszi, Jean Fontan, Mauricette Michallet, Alois Gratwohl, Giuseppe Milone, Chantal Doyen, Brigitte Pegourie, Roman Hajek, Philippe Casassus, Brigitte Kolb, Carine Chaleteix, Bernd Hertenstein, Francesco Onida, Heinz LudwigNicolas Ketterer, Christian Koenecke, Marleen Van Os, Mohamad Mohty, Andrew Cakana, Norbert Claude Gorin, Theo De Witte, Jean Luc Harousseau, Curly Morris, Gösta Gahrton

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Abstract

Purpose: This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide- dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods: Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). Results: Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 25%; P = .001), and the median duration of response was longer (17.2 v 13.4 months; P = .03). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. Conclusion: VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.

Original languageEnglish
Pages (from-to)2475-2482
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number20
DOIs
Publication statusPublished - Jul 10 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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