title: Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma.
abstract: The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1-7 and 15-21, 25 mg lenalidomide on days 1-21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed.
authors.affiliation: Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: D S
authors.identifier: 0000000236042574
authors.initials: DS
authors.lastname: Siegel
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Richardson
authors.affiliation: Department of Clinical Therapeutics, University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Dimopoulos
authors.affiliation: University Hospital, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Mitsiades
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Weber
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Houp
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gause
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vuocolo
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Eid
authors.affiliation: Pharmacyclics Inc., Sunnyvale, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Graef
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson