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
2012; Lippincott Williams & Wilkins; Volume: 30; Issue: 20 Linguagem: Inglês
10.1200/jco.2011.37.4918
ISSN1527-7755
AutoresLaurent Garderet, Simona Iacobelli, Philippe Moreau, Mamoun Dib, Ingrid Lafon, Dietger Niederwieser, Tamás Masszi, Jean Fontan, Mauricette Michallet, Aloïs Gratwohl, Giuseppe Milone, Chantal Doyen, Brigitte Pegourié, Roman Hájek, Philippe Casassus, Brigitte Kolb, Carine Chaleteix, Bernd Hertenstein, Francesco Onida, Heinz Ludwig, Nicolas Ketterer, Christian Koenecke, Marleen van Os, Mohamad Mohty, Andrew Cakana, Norbert Claude Gorin, Théo de Witte, Jean Luc Harousseau, Curly Morris, Gösta Gahrton,
Tópico(s)Protein Degradation and Inhibitors
ResumoThis 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).Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) 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).Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v13.8 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 21%; P 0.001), and the median duration of response was longer (17.9 v 13.4 months; P.04) [corrected].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.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.
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