title: Autologous transplantation and maintenance therapy in multiple myeloma.
abstract: BACKGROUND
  This open-label, randomized, phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan-prednisone-lenalidomide (MPR) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma.
  
  
  METHODS
  We randomly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction, and 251 patients to lenalidomide maintenance therapy or no maintenance therapy. The primary end point was progression-free survival.
  
  
  RESULTS
  The median follow-up period was 51.2 months. Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR (median progression-free survival, 43.0 months vs. 22.4 months; hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.32 to 0.61; P<0.001; and 4-year overall survival, 81.6% vs. 65.3%; hazard ratio for death, 0.55; 95% CI, 0.32 to 0.93; P=0.02). Median progression-free survival was significantly longer with lenalidomide maintenance than with no maintenance (41.9 months vs. 21.6 months; hazard ratio for progression or death, 0.47; 95% CI, 0.33 to 0.65; P<0.001), but 3-year overall survival was not significantly prolonged (88.0% vs. 79.2%; hazard ratio for death, 0.64; 95% CI, 0.36 to 1.15; P=0.14). Grade 3 or 4 neutropenia was significantly more frequent with high-dose melphalan than with MPR (94.3% vs. 51.5%), as were gastrointestinal adverse events (18.4% vs. 0%) and infections (16.3% vs. 0.8%); neutropenia and dermatologic toxic effects were more frequent with lenalidomide maintenance than with no maintenance (23.3% vs. 0% and 4.3% vs. 0%, respectively).
  
  
  CONCLUSIONS
  Consolidation therapy with high-dose melphalan plus stem-cell transplantation, as compared with MPR, significantly prolonged progression-free and overall survival among patients with multiple myeloma who were 65 years of age or younger. Lenalidomide maintenance, as compared with no maintenance, significantly prolonged progression-free survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00551928.).
authors.affiliation: From the Myeloma Unit, Division of Hematology, University of Turin (A.P., F.C., F.G., C. Cerrato, M.G., P.O., M.B.), and Unit of Clinical Epidemiology and Centro di Referimento per l'Epidemiologia-Piemonte, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino (A.E., G.C.), Turin, Division of Hematology, Ospedale Ferrarotto, Azienda Policlinico-Ospedale Vittorio Emanuele, University of Catania, Catania (F.D.R.), Hematology, Sapienza University of Rome (M.T.P.), and Cattedra di Ematologia, Ospedale S. Eugenio-University Tor Vergata (T.C.), Rome, Divisione di Ematologia, Ospedale S. Gerardo, Monza (S.P.), La Struttura Complessa di Ematologia, Dipartimento di Ematologia ed Oncologia, Azienda Ospedaliera Niguarda Ca' Granda (A.C.), Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute (M.M.), and Division of Hematology and Bone Marrow Transplantation, IRCCS Istituto Nazionale dei Tumori-University of Milan (P.C.), Milan, Ematologia, Policlinico Federico II, Naples (L.C.), Clinica di Ematologia, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona (M.O.), Unità Operativa Complessa Ematologia 1, IRCCS Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genoa (A.M.C.), Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna (E.Z., M.C.), Clinica Ematologia, Dipartimento di Scienze Mediche Sperimentali e Cliniche, Azienda Ospedaliera-Universitaria di Udine, Udine (F.P.), Scientific Direction, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (P.M.), and Struttura Complessa Ematologia e Dipartimento Oncologia Medica, Spedali Civili di Brescia, Brescia (C. Crippa) - all in Italy; and the Hematology Division, Hadassah University Hospital, Jerusalem (D.B.Y.), and the Hematology Institute, Chaim Sheba Medical Center, Tel Hashomer (E.R., A.N.) - both in Israel.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Dina
authors.initials: D
authors.lastname: Ben Yehuda
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Sara
authors.initials: S
authors.lastname: Pezzatti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerrato
authors.forename: Elena
authors.initials: E
authors.lastname: Ribakovsky
authors.forename: Mariella
authors.initials: M
authors.lastname: Genuardi
authors.forename: Anna
authors.initials: A
authors.lastname: Cafro
authors.forename: Magda
authors.initials: M
authors.lastname: Marcatti
authors.forename: Lucio
authors.initials: L
authors.lastname: Catalano
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Angelo Michele
authors.initials: AM
authors.lastname: Carella
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Andrea
authors.initials: A
authors.lastname: Evangelista
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Paola
authors.initials: P
authors.lastname: Omedé
authors.forename: Claudia
authors.initials: C
authors.lastname: Crippa
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D009503:Neutropenia / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone