title: Panobinostat: A histone deacetylase inhibitor for the treatment of relapsed or refractory multiple myeloma.
abstract: OBJECTIVE
  The mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, interaction potential, adverse effects, and place in therapy of panobinostat are reviewed.
  
  
  CONCLUSIONS
  Panobinostat (Farydak, Novartis) is a novel pan-deacetylase inhibitor approved for use in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least two regimens containing an immunomodulatory drug and bortezomib. National Comprehensive Cancer Network (NCCN) guidelines recommend the use of panobinostat plus bortezomib and dexamethasone as a preferred regimen for previously treated multiple myeloma (MM). A Phase III trial comparing panobinostat or placebo use in combination with bortezomib and dexamethasone demonstrated improved median progression-free survival in the panobinostat group (11.99 months [95% CI, 10.33-12.94 months] versus 8.08 months [95% CI, 7.56-9.23 months]; hazard ratio, 0.63 [95% CI, 0.52-0.76]; p < 0.0001), as well as a significantly higher rate of complete or near complete response (27.6% [95% CI, 23.2-32.4%] versus 15.7% [95% CI, 12.2-19.8%]; p = 0.00006). Common grade 3 or 4 laboratory abnormalities and adverse events associated with panobinostat include thrombocytopenia, lymphopenia, diarrhea, asthenia, fatigue, and peripheral neuropathy.
  
  
  CONCLUSIONS
  Panobinostat is a promising alternative to well-studied, NCCN-recommended regimens for the treatment of RRMM. It has demonstrated efficacy when used in combination with bortezomib and dexamethasone for the treatment of patients with MM who have received at least two prior regimens including bortezomib and an immunomodulatory agent. Despite the observed benefits, concern regarding toxicity may limit panobinostat use in practice.
authors.affiliation: Department of Pharmacy Practice, Belmont University College of Pharmacy, Nashville, TN. kristy.wahaib@belmont.edu.
authors.forename: Kristy
authors.initials: K
authors.lastname: Wahaib
authors.affiliation: Department of Pharmacy Practice, Belmont University College of Pharmacy, Nashville, TN.
authors.forename: Ashton E
authors.initials: AE
authors.lastname: Beggs
authors.affiliation: Department of Pharmacy Practice, Belmont University College of Pharmacy, Nashville, TN.
authors.forename: Hope
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Department of Pharmacy Practice, Belmont University College of Pharmacy, Nashville, TN.
authors.forename: Leela
authors.initials: L
authors.lastname: Kodali
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Ford
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000069286:Bortezomib / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D003907:Dexamethasone / Q000008:administration & dosage; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D000077767:Panobinostat; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000069286:Bortezomib; D003907:Dexamethasone; D000077767:Panobinostat