title: Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma.
abstract: BACKGROUND
  The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches.
  
  
  METHODS
  We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT.
  
  
  RESULTS
  The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers.
  
  
  CONCLUSIONS
  As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. (Funded by Intergroupe, Francophone du Myélome and Celgene; FIRST ClinicalTrials.gov number, NCT00689936; European Union Drug Regulating Authorities Clinical Trials number, 2007-004823-39.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: John
authors.initials: J
authors.lastname: Catalano
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.forename: Antonello
authors.initials: A
authors.lastname: Pinto
authors.forename: Katja
authors.initials: K
authors.lastname: Weisel
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Nizar
authors.initials: N
authors.lastname: Bahlis
authors.forename: Anne
authors.initials: A
authors.lastname: Banos
authors.forename: Mourad
authors.initials: M
authors.lastname: Tiab
authors.forename: Michel
authors.initials: M
authors.lastname: Delforge
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.forename: Catarina
authors.initials: C
authors.lastname: Geraldes
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: White
authors.forename: Daniel
authors.initials: D
authors.lastname: Binder
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anderson
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.forename: Jason
authors.initials: J
authors.lastname: Van Oostendorp
authors.forename: Christian
authors.initials: C
authors.lastname: Jacques
authors.forename: Annette
authors.initials: A
authors.lastname: Ervin-Haynes
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D011241:Prednisone / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone