title: A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma.
abstract: This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Larocca
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bringhen
authors.affiliation: Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Petrucci
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Oliva
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, Unità di Ematologia, San Giovanni Rotondo, Italy.
authors.forename: A P
authors.initials: AP
authors.lastname: Falcone
authors.affiliation: UOC Ematologia, Ospedale S Eugenio, Roma, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Caravita
authors.affiliation: Unit of Hematology and Stem Cell Transplantation, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (Pz), Italy.
authors.forename: O
authors.initials: O
authors.lastname: Villani
authors.affiliation: SC Ematologia, Dipartimento di Ematologia ed Oncologia, AO Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Benevolo
authors.affiliation: AO S Maria di Terni, SC Oncoematologia, Terni, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Liberati
authors.affiliation: UOC di Ematologia AO Cosenza, Cosenza, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Morabito
authors.affiliation: Department of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Montefusco
authors.affiliation: Division of Nuclear Medicine, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Passera
authors.affiliation: Hematology and SCT Unit, Osp SCamillo, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Rosa
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Omedé
authors.affiliation: Azienda Ospedaliera Bianchi Melacrino Morelli, Divisione di Ematologia, Reggio Calabria, Italy.
authors.forename: I D
authors.initials: ID
authors.lastname: Vincelli
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Spada
authors.affiliation: IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ponticelli
authors.affiliation: UO Ematologia e Centro Trapianti, Ospedale Oncologico di Riferimento Regionale 'Armando Businco', Cagliari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Derudas
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Genuardi
authors.affiliation: Divisione di Medicina Interna ed Ematologia, AUO San Luigi Gonzaga, Orbassano, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Guglielmelli
authors.affiliation: SODc Ematologia, AOU Careggi, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Nozzoli
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Aghemo
authors.affiliation: Division of Hematology, Department of Translational Medicine Amedeo Avogadro University, Ospedale Maggiore della Carità, Novara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Paoli
authors.affiliation: Division of Hematology, Azienda Policlinico-OVE, University of Catania, Catania, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Conticello
authors.affiliation: UOC Ematologia, Azienda Ospedaliera Universitaria, G Martino, Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Musolino
authors.affiliation: Clinica di Ematologia AOU Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Offidani
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Boccadoro
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage*; D003520:Cyclophosphamide; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage; D015996:Survival Rate
chemical_list: D000069286:Bortezomib; D003520:Cyclophosphamide; D008558:Melphalan; D011241:Prednisone