title: Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study.
abstract: Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP--notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.
authors.affiliation: Hematology Division, Grupo Español de MM, Spain. Paseo San Vicente 58-182; 37007 Salamanca, Spain.
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: José-M
authors.initials: JM
authors.lastname: Hernández
authors.forename: Miguel-T
authors.initials: MT
authors.lastname: Hernández
authors.forename: Norma-C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Marta
authors.initials: M
authors.lastname: Fuertes
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Juan-J
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: María-José
authors.initials: MJ
authors.lastname: Terol
authors.forename: Ana
authors.initials: A
authors.lastname: Sureda
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.forename: Paz
authors.initials: P
authors.lastname: Ribas
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.forename: Adrian
authors.initials: A
authors.lastname: Alegre
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Dolores
authors.initials: D
authors.lastname: Carrera
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Gemma
authors.initials: G
authors.lastname: Mateo
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Jesús-F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D016130:Immunophenotyping; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage*; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone