Panobinostat for the treatment of multiple myeloma

Abstract

Introduction: Multiple myeloma (MM) is a plasma cell disorder characterized by bone marrow suppression, skeletal complications, renal dysfunction and often a long course involving multiple different treatments. Over the past decade, novel treatment modalities have resulted in significant improvements in progression-free and overall survival. Histone deacetylase inhibitor(s) (HDACi) appear to offer an alternative therapeutic avenue in the treatment for MM likely through their impact on HDAC-6 function, and possibly through epigenetic effects as well. Panobinostat, a novel pan-HDAC (Pan-Dac) inhibitor, is of particular interest due to its broad HDAC inhibition, selectivity toward malignant cells and oral bioavailability.

Areas covered: In this review, the authors discuss the potential therapeutic benefits of panobinostat, in the treatment of MM. Topics covered include pleiotropic effects of HDAC modulation in MM, pharmacokinetics and pharmacodynamics of panobinostat, as well as available data demonstrating clinical efficacy and safety from clinical trials.

Expert opinion: Panobinostat is a novel Pan-Dac inhibitor with a number of different mechanisms of action related to its impact on myeloma. Data in combination with bortezomib suggests significant improvement in progression-free survival when compared with control treatment, as well as the ability to overcome bortezomib resistance. These factors suggest that the addition of panobinostat to our current treatment paradigm will offer new and important treatment options for our patients in all phases of myeloma treatment.

Keywords:

• histone deacetylase
• histone deacetylase inhibitors
• multiple myeloma
• panobinostat

Declaration of interest

S Lonial is a consultant for Millennium, Celgene, Novartis, Bristol-Myers Squibb and Onyx Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.