title: Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression.
abstract: BACKGROUND
  New treatment options offering enhanced activity in elderly, newly diagnosed patients with multiple myeloma are required. One strategy is to combine melphalan and prednisone with novel agents. We previously reported an 89% response rate, including 32% complete responses and 11% near complete responses, in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP) in 60 newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we report updated time-to-events data and the impact of poor prognosis factors on outcome.
  
  
  METHODS
  Updated analyses of time to biochemical progression and overall survival with VMP were conducted, and compared with those of historical controls treated with melphalan and prednisone. A univariate analysis was performed to evaluate the influence of known prognostic factors on the time to progression.
  
  
  RESULTS
  After a median follow-up of 26 months, the median time to progression with VMP was 27.2 months, compared with 20.0 months with melphalan plus prednisone. The median overall survival with VMP was not reached versus 26 months with melphalan and prednisone; the survival rate at 38 months was 85% versus 38%, respectively. Time to progression was not significantly affected by elevated beta(2)-microglobulin or lactate dehydrogenase levels, advanced age, or cytogenetic abnormalities, but was shorter in patients with albumin < 3 g/dL, Karnofsky performance status < or =70%, bone marrow plasma cell infiltration > or =40%, and, particularly, high plasma cell proliferative activity (> or = 2.5% S-phase cells).
  
  
  CONCLUSIONS
  VMP is highly active and well tolerated in elderly patients with newly diagnosed multiple myeloma, with 85% of patients alive at 3 years. Moreover, VMP may overcome the poor prognostic impact of various factors, particularly cytogenetic abnormalities.
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: José M
authors.initials: JM
authors.lastname: Hernández
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernández
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Marta
authors.initials: M
authors.lastname: Fuertes
authors.forename: Pedro
authors.initials: P
authors.lastname: Garcia-Sanchez
authors.forename: Juán J
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: María-José
authors.initials: MJ
authors.lastname: Terol
authors.forename: Ana
authors.initials: A
authors.lastname: Sureda
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.forename: Paz
authors.initials: P
authors.lastname: Ribas
authors.forename: Adrian
authors.initials: A
authors.lastname: Alegre
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Dolores
authors.initials: D
authors.lastname: Carrera
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Gemma
authors.initials: G
authors.lastname: Mateo
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
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; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone