Deacetylase inhibitors: an advance in myeloma therapy?

ABSTRACT

Introduction: 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.

KEYWORDS:

• Histone deacetylase inhibitor
• multiple myeloma
• panobinostat
• relapsed or relapsed and refractory
• ricolinostat

Declaration of interest

J P Laubach has served on advisory committees for Janssen and Millennium and has received payment for consulting to Novartis. J F San-Miguel has served on advisory committees or review panels for Celgene, Novartis, Janssen, Amgen, Millennium, Onyx, Bristol-Myers Squibb, and Merck Sharpe & Dohme. J Hou has received personal fees and non-financial support from Novartis. P Moreau has received personal fees from Novartis, Janssen, Celgene, Takeda, and Bristol-Myers Squibb. S Lonial has served on advisory committees for Novartis, Millennium, Celgene, Bristol-Myers Squibb, Janssen, and Onyx. H Einsele has received grants from Janssen, Amgen, Celgene, and Novartis. P G Richardson has received personal fees from Novartis, Takeda, Celgene and Johnson & Johnson and grants from Takeda and Celgene and has served on advisory committees for Novartis, Millennium Takeda, Janssen, Celgene, Bristol-Myers Squibb. 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 apart from those disclosed. Writing support, provided by Michael Demars, PhD (ArticulateScience LLC, Hamilton, NJ, USA) was utilized in the writing of this manuscript and was funded by Novartis Pharmaceuticals Corporation.​

Additional information

Funding

This paper was funded by Novartis Pharmaceuticals Corporation.