title: Deacetylase inhibitors: an advance in myeloma therapy?
abstract: A significant unmet need exists in patients with relapsed or refractory multiple myeloma (MM), which remains an incurable disease despite recent advances in the field. One such development was the use of deacetylase inhibitors (DACi), which exert unique antimyeloma effects through targeting of epigenetic and protein metabolism pathways. The pan-DACi panobinostat was recently approved in combination with bortezomib and dexamethasone for use in patients with relapsed or relapsed and refractory MM. Results of a phase 3 trial showed that the panobinostat-containing regimen improved the overall response rate and progression-free survival. Panobinostat-associated adverse events included thrombocytopenia, diarrhea, fatigue, and peripheral neuropathy. Research into how to maintain the benefits of DACi while improving tolerability is ongoing. Areas covered: This review focuses on the efficacy and safety of panobinostat and panobinostat-based combinations for MM. Early data from clinical trials investigating the HDAC6 inhibitor ricolinostat are also discussed. Expert commentary: DACi are a unique and effective new class of agents for the treatment of MM, with panobinostat being the first to have clinically meaningful benefit for patients with relapsed or refractory MM. Optimization of dose and schedule, novel combination strategies, and introduction of selective DACi may improve the risk-benefit profile of DACi-based regimens.
authors.affiliation: a Department of Hematologic Malignancies , Dana-Farber Cancer Institute , Boston , MA , USA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Laubach
authors.affiliation: b Department of Hematology , Clínica Universidad de Navarra, CIMA, IDISNA , Pamplona , Spain.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San-Miguel
authors.affiliation: c Department of Hematology/Oncology , Irmandade da Santa Casa de Misericordia de São Paulo , São Paulo , Brazil.
authors.forename: Vania
authors.initials: V
authors.lastname: Hungria
authors.affiliation: d Department of Hematology , Shanghai Changzheng Hospital , Shanghai , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.affiliation: e Department of Hematology , University Hospital of Nantes , Nantes , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: f Department of Hematology and Medical Oncology , Winship Cancer Institute of Emory University , Atlanta , GA , USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.affiliation: g Division of Hematology/Oncology , Gachon University Gil Medical Center , Incheon , South Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: h Department of Internal Medicine II , University Hospital Würzburg , Würzburg , Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: i Blood and Marrow Transplant Program , Moffitt Cancer Center , Tampa , FL , USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.affiliation: a Department of Hematologic Malignancies , Dana-Farber Cancer Institute , Boston , MA , USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000069286:Bortezomib / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic / Q000187:drug effects; 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; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077767:Panobinostat; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000069286:Bortezomib; D003907:Dexamethasone; D000077767:Panobinostat
keywords: Histone deacetylase inhibitor; multiple myeloma; panobinostat; relapsed or relapsed and refractory; ricolinostat