title: Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma.
abstract: Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade. Despite these advances, MM remains incurable and an unmet medical need remains for patients who are relapsed and/or refractory. Panobinostat is a potent, oral pan-deacetylase inhibitor that elicits anti-myeloma activity through epigenetic modulation of gene expression and disruption of protein metabolism. Preclinical data demonstrated that panobinostat has synergistic effects on myeloma cells when combined with bortezomib and dexamethasone. In a Phase III clinical trial evaluating bortezomib and dexamethasone in combination with panobinostat or placebo in patients with relapsed or relapsed and refractory MM (PANORAMA 1), panobinostat led to a significant increase in median progression-free survival. Panobinostat is currently under regulatory review with a recent accelerated approval granted for the treatment of relapsed disease, in which both bortezomib and immunomodulatory drugs have failed. Here, we summarize the preclinical, pharmacokinetic and clinical data for panobinostat in MM.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Laubach
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Vânia T M
authors.initials: VT
authors.lastname: Hungria
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San-Miguel
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077767:Panobinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000069286:Bortezomib; D003907:Dexamethasone; D000077767:Panobinostat
keywords: bortezomib; deacetylase inhibitors; multiple myeloma; panobinostat; treatment of relapsed and refractory disease