title: Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials.
abstract: Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis. Median cumulative bortezomib dose was higher in PETHEMA/GEM05 than VISTA (49.6 vs 37.0 mg/m2); median dose intensity was lower (2.0 vs 5.1 mg/m2/month). Median progression-free survival (PFS) and time-to-progression (TTP) were significantly longer in PETHEMA/GEM05 than VISTA (PFS, 30.5 vs 20.0 months, p = 0.0265; TTP, 33.8 vs 24.2 months, p = 0.0049) after a median follow-up of 77.2 and 26.0 months, respectively. Median overall survival (OS) was similar (61.3 vs 61.0 months, p = 0.6528; median follow-up, 77.6 vs 60.1 months). Post-induction complete response rate was lower in PETHEMA/GEM05 than VISTA (19 vs 31 %; p = 0.03318); on-study (including maintenance) rate was similar (30 vs 31 %; p = 0.89437). This analysis suggests that the less-intensive PETHEMA/GEM05 VMP regimen plus maintenance may improve PFS and TTP, but not OS, compared with the VISTA VMP regimen.
  
  
  BACKGROUND
  NCT00111319, NCT00443235.
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca, 37007, Spain. mvmateos@usal.es.
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Clinical Hematology Service and Oncohematological Clinical Trial Unit of the Institut Català d'Oncologia (ICO), Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital Universitario 12 de Octubre, S de Hematología HUNET-CRIS Unidad Ensayos Tempranos, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Martínez-López
authors.affiliation: Hospital Clínico Universitario de Valencia, Servicio de Hematología, Valencia, Spain.
authors.forename: Ana-Isabel
authors.initials: AI
authors.lastname: Teruel
authors.affiliation: Hospital de Donostia, Servicio de Hematología, Paseo Dr. Beguiristain 115, 20014, Donostia - San Sebastian (Guipúzcoa), Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Bengoechea
authors.affiliation: Servicio de Hematología, Hospital Clínico Universitario "Lozano Blesa" Zaragoza, Instituto de Investigación Sanitaria (ISS) de Aragón, Zaragoza, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Morales Meseguer, Murcia, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.affiliation: Oncology Clinical Research, Millennium Pharmaceuticals, Inc, Cambridge, MA, USA.
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.affiliation: Janssen Research & Development, High Wycombe, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Pei
authors.affiliation: Oncology Clinical Research, Millennium Pharmaceuticals, Inc, Cambridge, MA, USA.
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.affiliation: Department of Hematology, Clinica Universidad de Navarra-CIMA-IDSINA, Pamplona, Spain.
authors.forename: Jesus San
authors.initials: JS
authors.lastname: Miguel
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069286:Bortezomib / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008558:Melphalan / Q000008:administration & dosage*; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone
keywords: Bortezomib; Melphalan; Multiple myeloma; PETHEMA/GEM05; Prednisone; VISTA