title: Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial.
abstract: OBJECTIVE
  The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies.
  
  
  METHODS
  Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338).
  
  
  RESULTS
  With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide- (41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months.
  
  
  CONCLUSIONS
  VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse.
authors.affiliation: Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain.
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schlag
authors.forename: Nuriet K
authors.initials: NK
authors.lastname: Khuageva
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Martin
authors.initials: M
authors.lastname: Kropff
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.forename: Maria T
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Olga S
authors.initials: OS
authors.lastname: Samoilova
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Kudrat M
authors.initials: KM
authors.lastname: Abdulkadyrov
authors.forename: Rik
authors.initials: R
authors.lastname: Schots
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.forename: Dixie L
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002681:China; D005060:Europe; D005260:Female; D006801:Humans; D007557:Israel; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone