title: Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.
abstract: The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR.
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, Vrije Universiteit Medical Center, Amsterdam, The Netherlands;
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.affiliation: Hemato Oncologie Volwassenen Nederland Data Center, Erasmus Medical Center Cancer Center, Rotterdam, The Netherlands;
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.affiliation: Section of Hematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gotheborg, Sweden;
authors.forename: Ulf-Henrik
authors.initials: UH
authors.lastname: Mellqvist
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors.forename: Morten
authors.initials: M
authors.lastname: Salomo
authors.affiliation: Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands;
authors.forename: Gerard M J
authors.initials: GM
authors.lastname: Bos
authors.affiliation: Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands;
authors.forename: Mark-David
authors.initials: MD
authors.lastname: Levin
authors.affiliation: Hemato Oncologie Volwassenen Nederland Data Center, Erasmus Medical Center Cancer Center, Rotterdam, The Netherlands;
authors.forename: Heleen
authors.initials: H
authors.lastname: Visser-Wisselaar
authors.affiliation: Division of Hematology and Transfusion Medicine, Skane University Hospital, Lund, Sweden;
authors.forename: Markus
authors.initials: M
authors.lastname: Hansson
authors.affiliation: Department of Internal Medicine, Martini Ziekenhuis, Groningen, The Netherlands;
authors.forename: Annette W G
authors.initials: AW
authors.lastname: van der Velden
authors.affiliation: Department of Internal Medicine, Tergooi Ziekenhuizen, Blaricum, The Netherlands;
authors.forename: Wendy
authors.initials: W
authors.lastname: Deenik
authors.affiliation: Center of Hematology, Karolinska Institute, Stockholm, Sweden;
authors.forename: Astrid
authors.initials: A
authors.lastname: Gruber
authors.affiliation: Department of Internal Medicine, Isala, Zwolle, The Netherlands;
authors.forename: Juleon L L M
authors.initials: JL
authors.lastname: Coenen
authors.affiliation: Department of Hematology, Vejle Hopital, Vejle, Denmark;
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.affiliation: Department of Internal Medicine, Meander Medisch Centrum, Amersfoort, The Netherlands;
authors.forename: Saskia K
authors.initials: SK
authors.lastname: Klein
authors.affiliation: Department of Internal Medicine, Groene Hart Ziekenhuis, Gouda, The Netherlands;
authors.forename: Bea C
authors.initials: BC
authors.lastname: Tanis
authors.affiliation: Department of Oncology, Hematology and Palliative Care, Førde Central Hospital, Førde, Norway;
authors.forename: Damian L
authors.initials: DL
authors.lastname: Szatkowski
authors.affiliation: Department of Internal Medicine, Reinier de Graaf Ziekenhuis, Delft, The Netherlands;
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Brouwer
authors.affiliation: Department of Internal Medicine, Medisch Centrum Alkmaar, Alkmaar, The Netherlands;
authors.forename: Matthijs
authors.initials: M
authors.lastname: Westerman
authors.affiliation: Department of Internal Medicine, Maasstad Ziekenhuis, Rotterdam, The Netherlands;
authors.forename: M Rineke B L
authors.initials: MR
authors.lastname: Leys
authors.affiliation: Department of Internal Medicine, Jeroen Bosch Ziekenhuis, Den Bosch, The Netherlands;
authors.forename: Harm A M
authors.initials: HA
authors.lastname: Sinnige
authors.affiliation: Department of Hematology, Stavanger University Hospital, Stavanger, Norway;
authors.forename: Einar
authors.initials: E
authors.lastname: Haukås
authors.affiliation: Department of Internal Medicine, Zaans Medisch Centrum, Zaandam, The Netherlands;
authors.forename: Klaas G
authors.initials: KG
authors.lastname: van der Hem
authors.affiliation: Department of Internal Medicine, Tweesteden Ziekenhuis, Tilburg, The Netherlands;
authors.forename: Marc F
authors.initials: MF
authors.lastname: Durian
authors.affiliation: Department of Internal Medicine, Rijnstate Ziekenhuis, Arnhem, The Netherlands;
authors.forename: E Vera J M
authors.initials: EV
authors.lastname: Mattijssen
authors.affiliation: Department of Hematology, Cancer Center Amsterdam, Vrije Universiteit Medical Center, Amsterdam, The Netherlands;
authors.forename: Niels W C J
authors.initials: NW
authors.lastname: van de Donk
authors.affiliation: Department of Genetics, Radboud University Medical Center, Nijmegen, The Netherlands;
authors.forename: Marian J P L
authors.initials: MJ
authors.lastname: Stevens-Kroef
authors.affiliation: Department of Hematology, Erasmus Medical Center Cancer Center, Rotterdam, The Netherlands; and.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Hematology, St Olavs Hospital and Norwegian University of Science and Technology and KG Jebsen Myeloma Research Center, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone