title: Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
abstract: BACKGROUND
  The standard treatment for patients with multiple myeloma who are not candidates for high-dose therapy is melphalan and prednisone. This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy.
  
  
  METHODS
  We randomly assigned 682 patients to receive nine 6-week cycles of melphalan (at a dose of 9 mg per square meter of body-surface area) and prednisone (at a dose of 60 mg per square meter) on days 1 to 4, either alone or with bortezomib (at a dose of 1.3 mg per square meter) on days 1, 4, 8, 11, 22, 25, 29, and 32 during cycles 1 to 4 and on days 1, 8, 22, and 29 during cycles 5 to 9. The primary end point was the time to disease progression.
  
  
  RESULTS
  The time to progression among patients receiving bortezomib plus melphalan-prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan-prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P=0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P=0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%).
  
  
  CONCLUSIONS
  Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
authors.affiliation: Hospital Universitario Salamanca, CIC, IBMCC (USAL-CSIC), 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
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authors.lastname: Shpilberg
authors.forename: Martin
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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: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
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: Paul G
authors.initials: PG
authors.lastname: Richardson