title: Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.
abstract: This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787.
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.affiliation: Department of Cellular Biotechnology and Haematology, Sapienza University of Rome, Rome, Italy;
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Alessandra
authors.initials: A
authors.lastname: Larocca
authors.affiliation: Divisione di Ematologia, Ospedale Ferrarotto, Azienda Policlinico-OVE, Catania, Italy;
authors.forename: Concetta
authors.initials: C
authors.lastname: Conticello
authors.affiliation: Divisione di Ematologia, Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale Amedeo Avogadro, Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara, Novara, Italy;
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Valeria
authors.initials: V
authors.lastname: Magarotto
authors.affiliation: Scientific Direction, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy;
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Luana
authors.initials: L
authors.lastname: Boccadifuoco
authors.affiliation: Clinica di Ematologia, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Ancona, Italy;
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Omedé
authors.affiliation: Department of Cellular Biotechnology and Haematology, Sapienza University of Rome, Rome, Italy;
authors.forename: Fabiana
authors.initials: F
authors.lastname: Gentilini
authors.affiliation: Unit of Clinical Epidemiology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino and Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica-Piemonte, Torino, Italy;
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.affiliation: S.C. Ematologia, Dipartimento di Ematologia ed Oncologia, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, San Giovanni Battista, Torino, Italy;
authors.forename: Giulia
authors.initials: G
authors.lastname: Benevolo
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Mariella
authors.initials: M
authors.lastname: Genuardi
authors.affiliation: Ematologia, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milano, Italy;
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Stefania
authors.initials: S
authors.lastname: Oliva
authors.affiliation: Ematologia, Ospedale S. Eugenio, Rome, Italy;
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.affiliation: "Seràgnoli" Institute of Hematology, Bologna University School of Medicine, Bologna, Italy; and.
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.affiliation: Erasmus University Medical Center Cancer Institute, Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy;
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; C524865:carfilzomib; D003907:Dexamethasone; D003520:Cyclophosphamide