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, T. 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 & 10 others Nicolas Ketterer, Christian Koenecke, Marleen Van Os, Mohamad Mohty, Andrew Cakana, Norbert Claude Gorin, Theo De Witte, Jean Luc Harousseau, Curly Morris, Gösta Gahrton

Research output: Contribution to journalArticle

163 Citations (Scopus)

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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Thalidomide
Autologous Transplantation
Blood Group Antigens
Multiple Myeloma
Dexamethasone
Leukemia
Transplantation
Bone Marrow
Stem Cell Transplantation
Peripheral Nervous System Diseases
Survival Rate
Safety
Bortezomib
Incidence
Infection
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Journal of Clinical Oncology, Vol. 30, No. 20, 10.07.2012, p. 2475-2482.

Research output: Contribution to journalArticle

Garderet, L, Iacobelli, S, Moreau, P, Dib, M, Lafon, I, Niederwieser, D, Masszi, T, Fontan, J, Michallet, M, Gratwohl, A, Milone, G, Doyen, C, Pegourie, B, Hajek, R, Casassus, P, Kolb, B, Chaleteix, C, Hertenstein, B, Onida, F, Ludwig, H, Ketterer, N, Koenecke, C, Van Os, M, Mohty, M, Cakana, A, Gorin, NC, De Witte, T, Harousseau, JL, Morris, C & Gahrton, G 2012, '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', Journal of Clinical Oncology, vol. 30, no. 20, pp. 2475-2482. https://doi.org/10.1200/JCO.2011.37.4918
Garderet, Laurent ; Iacobelli, Simona ; Moreau, Philippe ; Dib, Mamoun ; Lafon, Ingrid ; Niederwieser, Dietger ; Masszi, T. ; Fontan, Jean ; Michallet, Mauricette ; Gratwohl, Alois ; Milone, Giuseppe ; Doyen, Chantal ; Pegourie, Brigitte ; Hajek, Roman ; Casassus, Philippe ; Kolb, Brigitte ; Chaleteix, Carine ; Hertenstein, Bernd ; Onida, Francesco ; Ludwig, Heinz ; Ketterer, Nicolas ; Koenecke, Christian ; Van Os, Marleen ; Mohty, Mohamad ; Cakana, Andrew ; Gorin, Norbert Claude ; De Witte, Theo ; Harousseau, Jean Luc ; Morris, Curly ; Gahrton, Gösta. / 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. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 20. pp. 2475-2482.
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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.",
author = "Laurent Garderet and Simona Iacobelli and Philippe Moreau and Mamoun Dib and Ingrid Lafon and Dietger Niederwieser and T. Masszi and Jean Fontan and Mauricette Michallet and Alois Gratwohl and Giuseppe Milone and Chantal Doyen and Brigitte Pegourie and Roman Hajek and Philippe Casassus and Brigitte Kolb and Carine Chaleteix and Bernd Hertenstein and Francesco Onida and Heinz Ludwig and Nicolas Ketterer and Christian Koenecke and {Van Os}, Marleen and Mohamad Mohty and Andrew Cakana and Gorin, {Norbert Claude} and {De Witte}, Theo and Harousseau, {Jean Luc} and Curly Morris and G{\"o}sta Gahrton",
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T1 - 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

T2 - The MMVAR/IFM 2005-04 randomized phase III trial from the chronic leukemia working party of the European Group for blood and marrow transplantation

AU - Garderet, Laurent

AU - Iacobelli, Simona

AU - Moreau, Philippe

AU - Dib, Mamoun

AU - Lafon, Ingrid

AU - Niederwieser, Dietger

AU - Masszi, T.

AU - Fontan, Jean

AU - Michallet, Mauricette

AU - Gratwohl, Alois

AU - Milone, Giuseppe

AU - Doyen, Chantal

AU - Pegourie, Brigitte

AU - Hajek, Roman

AU - Casassus, Philippe

AU - Kolb, Brigitte

AU - Chaleteix, Carine

AU - Hertenstein, Bernd

AU - Onida, Francesco

AU - Ludwig, Heinz

AU - Ketterer, Nicolas

AU - Koenecke, Christian

AU - Van Os, Marleen

AU - Mohty, Mohamad

AU - Cakana, Andrew

AU - Gorin, Norbert Claude

AU - De Witte, Theo

AU - Harousseau, Jean Luc

AU - Morris, Curly

AU - Gahrton, Gösta

PY - 2012/7/10

Y1 - 2012/7/10

N2 - 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.

AB - 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.

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