title: A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens.
abstract: Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (<minimal response) on a previous lenalidomide-containing regimen (lenalidomide non-responsive) or if they had progressive disease on or within 60 days of discontinuing a previous lenalidomide-containing regimen (lenalidomide relapsed/refractory). Patients received oral vorinostat 400 mg days 1-7 and 15-21, lenalidomide 25 mg days 1-21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28-day cycles. Twenty-five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression-free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre-treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide-refractory patients.
authors.affiliation: Rutgers New Jersey Medical School, Newark, NJ, USA.
authors.forename: Larysa
authors.initials: L
authors.lastname: Sanchez
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Richter
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Noa
authors.initials: N
authors.lastname: Biran
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bilotti
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: McBride
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Palka
authors.initials: P
authors.lastname: Anand
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ivanovski
authors.affiliation: Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D012074:Remission Induction; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D013792:Thalidomide; D000077337:Vorinostat; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: clinical trials; lenalidomide; multiple myeloma; myeloma therapy; vorinostat