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

• DOI: 10.1200/jco.2011.37.4918
• Publication Date: 2012-05-15T04:52:51Z
• Authors: 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 Ludwig; Nicolas Ketterer; Christian Koenecke; Marleen van Os; Mohamad Mohty; Andrew Cakana; Norbert Claude Gorin; Theo de Witte; Jean Luc Harousseau; Curly Morris; Gösta Gahrton
• Keywords: Adult; Male; Settore MED/01 - STATISTICA MEDICA; Transplantation, Autologous; Dexamethasone; Disease-Free Survival; Drug Administration Schedule; Bortezomib; 03 medical and health sciences; 0302 clinical medicine; Recurrence; Antineoplastic Combined Chemotherapy Protocols; Humans; Aged; ONCOL 3: Translational research NCMLS 2: Immune Regulation; Middle Aged; Boronic Acids; Thalidomide; 3. Good health; Treatment Outcome; Pyrazines; Female; Multiple Myeloma; Stem Cell Transplantation

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 21%; P = .001), and the median duration of response was longer (17.9 v 13.4 months; P = .04). 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.