Targeting histone deacetylases in T-cell lymphoma

Abstract

Histone deacetylase inhibitors (HDACi) are epigenetic modifiers with single-agent activity in patients with cutaneous and peripheral T-cell lymphoma (CTCL, PTCL). The mechanisms for this preferential activity remain unclear, and although some would term this as ‘class effect,’ there are differences in efficacy and safety, likely a result of the varying chemical structures/classes, histone and non-histone targets, potencies, and clinical dosing for each. Three HDACi have single-agent approval in relapsed/refractory TCL in the United States: romidepsin in CTCL and PTCL, vorinostat in CTCL, and belinostat in PTCL. Although comparison of these agents is difficult due to differences in patient populations, through this review we aimed to provide a detailed overview of the clinical data for HDACi in TCL and their use in clinical practice. Despite early concerns, data demonstrate the cardiac safety of HDACi, while highlighting the need to maintain electrolytes in the normal range and monitor QT interval when initially co-administering antiemetics or other drugs that prolong QT. To further improve response rates and durability of responses, HDACi are under clinical investigation in combination with chemotherapy regimens and various novel agents.

Keywords:

• Romidepsin
• vorinostat
• belinostat
• chidamide
• panobinostat
• T-cell lymphoma

Acknowledgements

The authors take full responsibility for the content of this manuscript but thank William Ho, PhD (MediTech Media), for providing medical editorial assistance. Financial support for medical editorial assistance was provided by Celgene Corporation. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1247956.