Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma

Expert Rev Anticancer Ther. 2015;15(7):737-48. doi: 10.1586/14737140.2015.1047770. Epub 2015 Jun 7.

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.

Keywords: bortezomib; deacetylase inhibitors; multiple myeloma; panobinostat; treatment of relapsed and refractory disease.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bortezomib / administration & dosage
  • Clinical Trials as Topic
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Histone Deacetylase Inhibitors / adverse effects
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Hydroxamic Acids / adverse effects
  • Hydroxamic Acids / pharmacology*
  • Hydroxamic Acids / therapeutic use
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Panobinostat

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Indoles
  • Bortezomib
  • Dexamethasone
  • Panobinostat