title: Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma.
abstract: Research has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti-multiple myeloma (MM) activity. This phase I dose-escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or 20/27 mg/m(2) ; 30-min infusion; days 1, 2, 8, 9, 15, 16), lenalidomide (15 or 25 mg; days 1-21), vorinostat (300 or 400 mg; days 1-7, 15-21), and dexamethasone (40 mg; days 1, 8, 15, 22) in 28-d cycles. No dose-limiting toxicities were observed; the maximum tolerated dose was not reached. The maximum administered dose was carfilzomib 20/27 mg/m(2) , lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow-up of 10 months, median progression-free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM.
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bilotti
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Richter
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: McNeill
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: McBride
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Raucci
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Palka
authors.initials: P
authors.lastname: Anand
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Urszula
authors.initials: U
authors.lastname: Bednarz
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ivanovski
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Smith
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Batra
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Aleman
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Taliah
authors.initials: T
authors.lastname: Sims
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Guerrero
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mato
authors.affiliation: Multiple Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D009842:Oligopeptides; D013792:Thalidomide; D000077337:Vorinostat; C524865:carfilzomib; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: clinical studies; clinical trials; experimental therapies; multiple myeloma; myeloma therapy