title: Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma.
abstract: OBJECTIVE
  This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies.
  
  
  METHODS
  In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients.
  
  
  RESULTS
  After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates.
  
  
  CONCLUSIONS
  VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP.
authors.affiliation: Hospital Universitario Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain. sanmigiz@usal.es
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
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 Teresa
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: Michel
authors.initials: M
authors.lastname: Delforge
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: William
authors.initials: W
authors.lastname: Deraedt
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D016017:Odds Ratio; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012306:Risk; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D001897:Boronic Acids; D011719:Pyrazines; D001613:beta 2-Microglobulin; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone