Emerging role of the histone deacetylase inhibitor romidepsin in hematologic malignancies

Importance of the field: Histone acetylation plays a crucial role in chromatin modification and the regulation of gene expression. Histone deacetylase inhibitors (HDACi) are a novel class of antitumor agents with pleiotropic effects; they are under active clinical investigation. The HDACi romidepsin is being evaluated in a variety of tumors and was recently approved for the treatment of cutaneous T-cell lymphomas (CTCL). Areas covered in this review: This review focuses on the findings from early Phase trials involving romidepsin, and the Phase II trial results that led to the approval of romidepsin in CTCL. What the reader will gain: Mechanisms of action of HDACi, including romidepsin, are described in this review and the pharmacodynamic and pharmacokinetic properties of romidepsin are summarized. The efficacy and safety profile of romidepsin in clinical trials in T-cell lymphoma is reviewed, and emerging data on single-agent and combination strategies in myeloid and B-lymphoid malignancies is outlined. Take home message: Romidepsin has significant activity and an acceptable safety profile in CTCL and peripheral T-cell lymphomas. Its use in rationally designed combination approaches is under active investigation in B-lymphoid malignancies.