title: Panobinostat for the Treatment of Multiple Myeloma.
abstract: Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received ≥2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression-free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P < 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Laubach
authors.affiliation: Nantes University Hospital, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San-Miguel
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. paul_richardson@dfci.harvard.edu.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000077767:Panobinostat; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat