Document Detail


Continuous lenalidomide treatment for newly diagnosed multiple myeloma.
MedLine Citation:
PMID:  22571200     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Antonio Palumbo; Roman Hajek; Michel Delforge; Martin Kropff; Maria Teresa Petrucci; John Catalano; Heinz Gisslinger; Wiesław Wiktor-Jędrzejczak; Mamia Zodelava; Katja Weisel; Nicola Cascavilla; Genadi Iosava; Michele Cavo; Janusz Kloczko; Joan Bladé; Meral Beksac; Ivan Spicka; Torben Plesner; Joergen Radke; Christian Langer; Dina Ben Yehuda; Alessandro Corso; Lindsay Herbein; Zhinuan Yu; Jay Mei; Christian Jacques; Meletios A Dimopoulos;
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  366     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-10     Completed Date:  2012-05-17     Revised Date:  2013-08-22    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1759-69     Citation Subset:  AIM; IM    
Affiliation:
Myeloma Unit, Division of Hematology, University of Turin, Azienda Ospedaliero-Universitaria, S. Giovanni Battista, Via Genova 3, 10126 Turin, Italy. appalumbo@yahoo.com
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00405756
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / adverse effects,  therapeutic use*
Disease-Free Survival
Double-Blind Method
Female
Follow-Up Studies
Humans
Induction Chemotherapy
Kaplan-Meier Estimate
Maintenance Chemotherapy
Male
Melphalan / administration & dosage*,  adverse effects
Multiple Myeloma / drug therapy*,  mortality
Neoplasms, Second Primary / epidemiology
Neutropenia / chemically induced
Prednisone / administration & dosage*,  adverse effects
Thalidomide / administration & dosage,  adverse effects,  analogs & derivatives*
Chemical
Reg. No./Substance:
148-82-3/Melphalan; 191732-72-6/lenalidomide; 50-35-1/Thalidomide; 53-03-2/Prednisone
Investigator
Investigator/Affiliation:
B Augustson / ; N Horvath / ; D Joshua / ; P Mollee / ; M Prince / ; A Spencer / ; K Taylor / ; A G Gastl / ; R Greil / ; H Ludwig / ; I Iskrov / ; A Uss / ; G Fillet / ; R Schots / ; J van Droogenbroeck / ; V Maisnar / ; V Scudla / ; H Gregersen / ; M Attal / ; J P Fermand / ; A Jaccard / ; M Macro / ; J -F Rossi / ; G Dölken / ; M Engelhardt / ; H Goldschmidt / ; S Knop / ; D Niederwieser / ; G Crotty / ; A Nagler / ; J Rowe / ; O Shpilberg / ; A M Cafro / ; T Caravita / ; R Foa / ; M Gobbi / ; S Zweegman / ; A Dmoszynska / ; A Hellmann / ; A B Skotnicki / ; K Abdulkadyrov / ; N Domnikova / ; E Osmanov / ; V Rossiev / ; O Rukavistin / ; A Alegre / ; F J Capote / ; M L Martino / ; J S Miguel / ; T Ahlgren / ; S Bauer / ; F Stenner / ; S Cagirgan / ; S Schey / ; K Yong / ; P Kaplan / ; E Kyeting / ; T Lysa / ; Z Maslyak / ; G Pylypenko / ; N Tretyak /
Comments/Corrections
Comment In:
N Engl J Med. 2012 Aug 9;367(6):573; author reply 573-5   [PMID:  22873542 ]
N Engl J Med. 2012 May 10;366(19):1836-8   [PMID:  22571206 ]
Internist (Berl). 2013 Jul;54(7):892-6   [PMID:  23748490 ]
Erratum In:
N Engl J Med. 2012 Jul 19;367(3):285

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  TGF-? sensitivity is determined by N-linked glycosylation of the type II TGF-? receptor.
Next Document:  Lenalidomide after stem-cell transplantation for multiple myeloma.