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Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review

Authors Makita S, Maeshima AM, Maruyama D, Izutsu K, Tobinai K

Received 19 December 2017

Accepted for publication 26 March 2018

Published 20 April 2018 Volume 2018:11 Pages 2287—2293


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Shinichi Makita,1 Akiko Miyagi Maeshima,2 Dai Maruyama,1 Koji Izutsu,1 Kensei Tobinai1

Department of Hematology, 2Department of Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan

Abstract: T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL) generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor), brentuximab vedotin (antibody–drug conjugate targeting CD30), chidamide (histone deacetylase inhibitor), and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody), have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients), which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL. However, it is necessary to appropriately manage opportunistic infections and secondary lymphomas possibly associated with long-lasting lymphocytopenia caused by forodesine. In this manuscript, we have summarized the currently available evidence for forodesine and discussed the clinical implications for PTCL treatment.

forodesine, PTCL, T-cell lymphoma, new agents, lymphoma, non-Hodgkin lymphoma, PNP, purine nucleoside phosphorylase

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