title: Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma.
abstract: BACKGROUND
  For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention.
  
  
  METHODS
  In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety.
  
  
  RESULTS
  After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; P<0.001). The 3-year survival rate was also higher in the treatment group (94% vs. 80%; hazard ratio for death, 0.31; 95% CI, 0.10 to 0.91; P=0.03). A partial response or better was achieved in 79% of patients in the treatment group after the induction phase and in 90% during the maintenance phase. Toxic effects were mainly grade 2 or lower.
  
  
  CONCLUSIONS
  Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.).
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca-Consejo Superior de Investigaciones Científicas, Salamanca, Spain.
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Miguel-Teodoro
authors.initials: MT
authors.lastname: Hernández
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.forename: Lucía
authors.initials: L
authors.lastname: López Corral
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.forename: Javier
authors.initials: J
authors.lastname: López
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarría
authors.forename: Nuria
authors.initials: N
authors.lastname: Quintana
authors.forename: José-Luis
authors.initials: JL
authors.lastname: García
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Jesús-F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D012306:Risk; D015996:Survival Rate; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide