The discovery and development of romidepsin for the treatment of T-cell lymphoma

ABSTRACT

Introduction: Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34–35% and 25–38%, with complete response (CR) rates of 6% and 15–18%, respectively.

Areas covered: This review summarizes the development of romidepsin, the mechanisms behind its antineoplastic action and its pharmacology. It also covers its pharmacokinetic and pharmacodynamic properties, as well as the preclinical and clinical data on its activity in T-cell lymphoma.

Expert opinion: Since there are only few effective therapies available for T-cell lymphomas, romidepsin is a valuable option for relapsed/refractory patients with both CTCL and PTCL. It’s also generally well tolerated, and gives potentially durable responses for patients with advanced and symptomatic disease. Combinations of romidepsin with other antineoplastic agents may also further improve drug response and outcomes in T-cell lymphoma.

KEYWORDS:

• Romidepsin
• Istodax
• FR901228
• depsipetide
• T-cell lymphoma
• PTCL
• CTCL

Article Highlights

• Romidepsin is an antineoplastic, epigenetic modifying agent, derived from a Chromobacterium violaceum bacterium culture, and belongs to the group of selective histone deacetylase inhibitors

• The mechanism of romidepsin’s antineoplastic action encompasses cell cycle arrest, programmed cell death and the inhibition of angiogenesis

• Based on phase II pivotal clinical trials, romidepsin has been approved by the U.S. FDA for treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL)

• Romidepsin is more effective when compared with previous standard therapies and can produce durable responses in T-cell lymphoma

• Patients receiving romidepsin may be exposed to different non-hematological (the major concern being cardiac toxicity) and hematological adverse events (mainly leukopenia, granulocytopenia, and thrombocytopenia), which in the majority of patients are manageable

• A combination of romidepsin with standard chemotherapy or other recently implemented biologic treatments are promising therapeutic options for T-cell lymphoma patients

This box summarizes key points contained in the article.

Acknowledgments

We thank Mr Edward Lowczowski from the Medical University of Lodz for editorial assistance.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was not utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by the grants from the Medical University of Lodz, Poland (No. 503/8-093-01/503-81-001 and No. 502-03/8-093-01/502-64-060, and No. 503/1-1093-01/503-01).