title: Continuous lenalidomide treatment for newly diagnosed multiple myeloma.
abstract: BACKGROUND
  Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma.
  
  
  METHODS
  We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival.
  
  
  RESULTS
  The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP.
  
  
  CONCLUSIONS
  MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.).
authors.affiliation: Myeloma Unit, Division of Hematology, University of Turin, Azienda Ospedaliero-Universitaria, S. Giovanni Battista, Via Genova 3, 10126 Turin, Italy. appalumbo@yahoo.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.forename: Michel
authors.initials: M
authors.lastname: Delforge
authors.forename: Martin
authors.initials: M
authors.lastname: Kropff
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: John
authors.initials: J
authors.lastname: Catalano
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Wiesław
authors.initials: W
authors.lastname: Wiktor-Jędrzejczak
authors.forename: Mamia
authors.initials: M
authors.lastname: Zodelava
authors.forename: Katja
authors.initials: K
authors.lastname: Weisel
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
authors.forename: Genadi
authors.initials: G
authors.lastname: Iosava
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.forename: Joergen
authors.initials: J
authors.lastname: Radke
authors.forename: Christian
authors.initials: C
authors.lastname: Langer
authors.forename: Dina
authors.initials: D
authors.lastname: Ben Yehuda
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corso
authors.forename: Lindsay
authors.initials: L
authors.lastname: Herbein
authors.forename: Zhinuan
authors.initials: Z
authors.lastname: Yu
authors.forename: Jay
authors.initials: J
authors.lastname: Mei
authors.forename: Christian
authors.initials: C
authors.lastname: Jacques
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D009503:Neutropenia / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone