Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: pharmacology and clinical outcomes

Expert Rev Clin Pharmacol. 2016;9(1):35-48. doi: 10.1586/17512433.2016.1096773. Epub 2015 Oct 26.

Abstract

Recently, outcomes for patients with multiple myeloma have improved dramatically due to improved and innovative therapies. However, most patients will either relapse or become refractory to current therapy. Thus, a significant unmet need remains for novel agents to treat this patient population. Panobinostat, a potent pan-deacetylase inhibitor with a unique mechanism of action targeting both epigenetic regulation of gene expression and protein metabolism, has preclinical synergy with a number of agents, including the proteasome inhibitor bortezomib. In a phase 3 trial of panobinostat with bortezomib and dexamethasone, addition of panobinostat significantly prolonged the median progression-free survival of patients with relapsed or relapsed and refractory multiple myeloma. This review focuses on clinical development of panobinostat, with particular emphasis on pharmacokinetics and adverse event management.

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

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease-Free Survival
  • Epigenesis, Genetic
  • Histone Deacetylase Inhibitors / adverse effects
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Hydroxamic Acids / adverse effects
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use*
  • Indoles / adverse effects
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Panobinostat
  • Recurrence

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Indoles
  • Panobinostat