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Clinical developments in the treatment of relapsed or relapsed and refractory multiple myeloma: impact of panobinostat, the first-in-class histone deacetylase inhibitor

Authors Redic K, Hough S, Price E

Received 16 December 2015

Accepted for publication 2 March 2016

Published 10 May 2016 Volume 2016:9 Pages 2783—2793


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Dekuang Zhao

Peer reviewer comments 3

Editor who approved publication: Professor Min Li

Kimberly A Redic,1 Shannon M Hough,2 Erika M Price1

1College of Pharmacy, University of Michigan, 2Department of Pharmaceutical Services, University of Michigan Health System, Ann Arbor, MI, USA

Background: Panobinostat is a new agent for the treatment of relapsed and refractory multiple myeloma (rrMM) as part of a combination regimen. This article presents an overview of the mechanism of action, pharmacokinetics, safety, efficacy, patient care strategies, and role of the agent in treating rrMM patients.
Results: Panobinostat belongs to the class of drugs known as histone deacetylase inhibitors, and has high activity against Class I, II, and IV nonhistone deacetylases and histone deacetylases. It represents the first of its class to receive approval for use in MM, and received priority review and orphan drug status in both US and Europe, when used in combination with bortezomib and dexamethasone in the treatment of rrMM. Approval of panobinostat was based on subgroup analysis of Phase III data obtained in the PANORAMA trial program for evaluation of the combination of panobinostat, bortezomib, and dexamethasone. Additional clinical trials have continued to explore optimal dosing regimens and novel combination regimens to further clarify the optimal role of panobinostat in the arsenal of drugs for rrMM. Panobinostat has shown a manageable safety profile characterized primarily by hematologic toxicities (thrombocytopenia, neutropenia, lymphopenia, and anemia), gastrointestinal toxicities, notably diarrhea and nausea, as well as fatigue/asthenia, electrolyte abnormalities, and less commonly cardiac toxicities.
Conclusion: Panobinostat represents an important addition to the treatment armamentarium for patients with rrMM, and studies are underway evaluating its optimal dosing strategy and role in combination with other drugs used to treat this patient population.

Keywords: panobinostat, multiple myeloma, LBH589, relapsed-refractory, Farydak, HDAC

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