title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
authors.forename: Avinash
authors.initials: A
authors.lastname: Desai
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D017326:Clinical Trials, Phase III as Topic; D003907:Dexamethasone / Q000008:administration & dosage; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin