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J Clin Oncol. 2013 Sep 10;31(26):3279-87. doi: 10.1200/JCO.2012.48.4626. Epub 2013 Jul 29.

Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials.

Author information

1
Pieter Sonneveld, Erasmus Medical Center, Rotterdam; Henk M. Lokhorst, Utrecht Medical Center, Utrecht, the Netherlands; Hartmut Goldschmidt, University Hospital of Heidelberg, Heidelberg, Germany; Laura Rosiñol, Joan Bladé, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona; Juan José Lahuerta, Hospital Universitario 12 de Octubre, Madrid, Spain; Michele Cavo, Paola Tacchetti, Elena Zamagni, Istituto di Ematologia Seràgnoli, Università degli Studi di Bologna, Bologna, Italy; Michel Attal, Hopital Purpan, Toulouse; Philippe Moreau, University Hospital, Nantes, France; Avinash Desai, Janssen Global Services; Kevin Liu, Janssen Research and Development, Raritan, NJ; Dixie-Lee Esseltine, Millennium Pharmaceuticals, Cambridge, MA; Andrew Cakana, Janssen Research and Development, High Wycombe, United Kingdom; Helgi van de Velde, Janssen Research and Development, Beerse, Belgium.

Abstract

PURPOSE:

To characterize efficacy and safety of bortezomib-based versus nonbortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma.

PATIENTS AND METHODS:

Patient-level data from the IFM 2005-01 (bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis. Key efficacy end points were post-transplantation complete plus near-complete response (CR+nCR) rate and progression-free survival (PFS).

RESULTS:

Patient-level data for 1,572 patients (bortezomib-based induction, n = 787; nonbortezomib-based induction, n = 785) were included. Post-transplantation CR+nCR rate was significantly higher following bortezomib-based versus nonbortezomib-based induction (38% v 24%; odds ratio, 2.05; P < .001); the benefit remained similar (pooled odds ratio, 1.96) when GIMEMA MM-BO2005 data were included. Median PFS was 35.9 months versus 28.6 months with bortezomib-based versus nonbortezomib-based induction, respectively (hazard ratio, 0.75; P < .001); 3-year overall survival (OS) rates were 79.7% and 74.7%, respectively (hazard ratio for OS, 0.81; P = .0402). Median duration of induction treatment was 11 weeks in both treatment groups. Rates of peripheral neuropathy during induction were 34% versus 17% (grade ≥ 3, 6% v 1%). Overall, 3% and 4% of patients died during bortezomib-based and nonbortezomib-based induction, respectively.

CONCLUSION:

Bortezomib-based induction results in significant improvements in response and PFS/OS compared with nonbortezomib-based induction and is generally well tolerated, with a higher rate of peripheral neuropathy but no apparent increase in risk of death during induction.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00200681 NCT00461747 NCT01134484.

PMID:
23897961
DOI:
10.1200/JCO.2012.48.4626
[Indexed for MEDLINE]

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