Objective: The pharmacology, pharmacokinetic and pharmacodynamic properties, and clinical data on a novel therapy for the treatment of cutaneous or peripheral T-cell lymphoma (CTCL, PTCL) are summarized.

Conclusions: Romidepsin is the only bicyclic histone deacetylase (HDAC) inhibitor to undergo clinical development. A potent and specific inhibitor of class 1 HDACs, romidepsin has linear pharmacokinetics and is primarily metabolized by cytochrome P-450 isoenzyme 3A4. In two Phase II studies involving patients with relapsed or refractory CTCL, romidepsin therapy produced overall response rates of 34-35% (including patients with advanced and heavily pretreated disease), with a complete response seen in about 6% of patients in both studies; romidepsin responses were seen across all evaluated disease sites (skin, blood, lymph, viscera). In two Phase II studies in patients with relapsed or refractory PTCL, romidepsin produced overall response rates of 25-38%, and 15-18% of patients experienced a complete response; therapeutic responses were seen across major PTCL subtypes regardless of the number or types of previous therapies or refractoriness to the last prior therapy. In clinical trials to date, romidepsin therapy was generally well tolerated, with nausea, fatigue, and vomiting reported as the most common nonhematologic adverse events. However, thrombocytopenia and neutropenia are relatively common events, especially in patients with PTCL. Conclusions: Romidepsin, a class 1-specific HDAC inhibitor, induces durable responses, with a manageable toxicity profile, in patients with relapsed or refractory CTCL or PTCL who have few therapeutic options.