title: Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial.
abstract: The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m2on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2-3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).
authors.affiliation: Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rosiñol
authors.affiliation: Department of Hematology, Hospital Germans Trias I Pujol, Badalona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Department of Hematology, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Teruel
authors.affiliation: Department of Hematology, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: A L
authors.initials: AL
authors.lastname: de la Guía
authors.affiliation: Department of Hematology, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: MaJ
authors.initials: M
authors.lastname: Blanchard
authors.affiliation: Department of Hematology, Hospital La Fe, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: de la Rubia
authors.affiliation: Department of Hematology, Hospital de la Santa Creu i Sant Pau,Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Granell
authors.affiliation: Department of Hematology, Complejo Asistencial Son Espases, Palma de Mallorca, Spain.
authors.forename: MaA
authors.initials: M
authors.lastname: Sampol
authors.affiliation: Department of Hematology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Palomera
authors.affiliation: Department of Hematology, Hospital Universitari Josep Trueta, Girona,Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: González
authors.affiliation: Department of Hematology, Hospital de Donostia, Donostia, Spain.
authors.forename: MaA
authors.initials: M
authors.lastname: Etxebeste
authors.affiliation: Department of Hematology, Hospital Clínico Universitario San Carlos, Madrid,Spain.
authors.forename: R
authors.initials: R
authors.lastname: Martínez-Martínez
authors.affiliation: Department of Hematology, Hospital Universitario de Canarias, La Laguna, Spain.
authors.forename: M T
authors.initials: MT
authors.lastname: Hernández
authors.affiliation: Department of Hematology, Hospital Morales Messeguer, Murcia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: de Arriba
authors.affiliation: Department of Hematology, Hospital La Princesa, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alegre
authors.affiliation: Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: MaT
authors.initials: M
authors.lastname: Cibeira
authors.affiliation: Department of Hematology, Hospital Clínico Universitario de Salamanca, Salamanca, Spain.
authors.forename: MaV
authors.initials: M
authors.lastname: Mateos
authors.affiliation: Department of Hematology, Hospital Universitario 12 de Octubre,Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-López
authors.affiliation: Department of Hematology, Hospital Universitario 12 de Octubre,Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Department of Hematology, Clínica Universitaria de Navarra, Pamplona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: San Miguel
authors.affiliation: Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bladé
mesh_terms: D000069286:Bortezomib / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage*
chemical_list: D016898:Interferon-alpha; D013792:Thalidomide; D000069286:Bortezomib