Targeting histone deacetylases in T-cell lymphoma
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Updated: Mar 12, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Alison J Moskowitz1, Steven M Horwitz1
1a Memorial Sloan Kettering Cancer Center , New York , NY , USA.
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.
Insights
Histone deacetylase inhibitors (HDACi) show efficacy in T-cell lymphomas. While cardiac safety is confirmed, monitoring electrolytes and QT intervals is crucial for patients on HDACi therapy.
Area of Science:
- Oncology
- Pharmacology
- Epigenetics
Background:
- Histone deacetylase inhibitors (HDACi) are epigenetic modifiers with demonstrated single-agent activity in T-cell lymphomas (TCL).
- The precise mechanisms underlying this activity and variations in efficacy and safety among different HDACi remain incompletely understood.
- Three HDACi—romidepsin, vorinostat, and belinostat—are approved for relapsed/refractory TCL in the US.
Purpose of the Study:
- To provide a comprehensive review of clinical data for HDACi in TCL.
- To detail the use of HDACi in clinical practice for TCL management.
- To elucidate the efficacy and safety profiles of approved HDACi.
Main Methods:
- Review of clinical trial data for HDACi in cutaneous and peripheral T-cell lymphoma (CTCL, PTCL).
- Analysis of efficacy, safety, and dosing information for romidepsin, vorinostat, and belinostat.
- Examination of factors influencing HDACi activity, including chemical structure and targets.
Main Results:
- HDACi demonstrate single-agent activity in CTCL and PTCL.
- Clinical data confirm the cardiac safety of HDACi, with recommendations for electrolyte and QT interval monitoring.
- Differences in efficacy and safety are attributed to variations in chemical structures, targets, and dosing.
Conclusions:
- HDACi are valuable agents in the treatment of relapsed/refractory TCL.
- Maintaining electrolyte balance and monitoring QT intervals are important considerations during HDACi therapy.
- Ongoing research is exploring combination therapies involving HDACi to enhance treatment outcomes.
