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Chidamide in the treatment of peripheral T-cell lymphoma

Authors Chan TS, Tse E, Kwong YL

Received 13 April 2016

Accepted for publication 6 July 2016

Published 12 January 2017 Volume 2017:10 Pages 347—352

DOI https://doi.org/10.2147/OTT.S93528

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Professor Min Li

Thomas S Chan, Eric Tse, Yok-Lam Kwong

Department of Medicine, Queen Mary Hospital, Hong Kong, People’s Republic of China

Abstract: Mature T-cell lymphomas are aggressive malignancies. Treatment outcome is poor with conventional chemotherapy. They are about twice as common in Asia as compared with other non-Asian countries. Histone proteins form the basic structure of chromatin, and their acetylation at lysine residues relaxes chromatin structure, facilitating gene transcription. Conversely, histone deacetylation, catalyzed by histone deacetylases, compacts chromatin and represses gene transcription. Histone deacetylase inhibitors are an important class of antineoplastic agents. Chidamide is a novel orally active benzamide-type histone deacetylase inhibitor that has shown in vitro activities against a wide array of neoplasms. In Phase I trials, chidamide showed preferential efficacy in mature T-cell lymphomas. In a pivotal Phase II trial of chidamide in 79 patients with relapsed or refractory mature T-cell lymphomas, an overall response rate of 28% (complete remission/complete remission unconfirmed: 14%) was achieved, with most responses occurring within the first 6 weeks of treatment. The median duration of response (DOR) was 9.9 (1.1–40.8) months. Of 22 responders, 19 patients (86%) had a DOR of ≥3 months and eight patients (36%) had a DOR of >12 months. Angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma (anaplastic lymphoma kinase-negative) showed better response rates, with the most durable responses observed in angioimmunoblastic T-cell lymphoma patients. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. Chidamide is approved by the China Food and Drug Administration for the treatment of relapsed and refractory peripheral T-cell lymphomas.

Keywords:
chidamide, peripheral T-cell lymphoma, benzamide, histone deacetylase inhibitors

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