Development of new agents for peripheral T-cell lymphoma

ABSTRACT

Introduction: Peripheral T-cell lymphoma (PTCL) is a relatively rare, heterogeneous group of mature T-cell neoplasms generally associated with poor prognosis, partly because of refractoriness against conventional cytotoxic chemotherapies. To improve the outcome of patients with PTCL, the clinical development of several novel agents is currently under investigation.

Areas covered: Since the first approval of pralatrexate (dihydrofolate reductase inhibitor) by the US Food and Drug Administration, belinostat, romidepsin (histone deacetylase inhibitors), and brentuximab vedotin (anti-CD30 antibody-drug conjugate) have been approved in the US, and many other countries. In addition, mogamulizumab (anti-CC chemokine receptor 4 antibody), chidamide (histone deacetylase inhibitor), and forodesine (purine nucleoside phosphorylase inhibitor) have been approved in Asian countries, including China, and Japan. In this review, we have summarized the available data regarding these approved agents and new agents currently under development for PTCL.

Expert opinion: Novel agents will be a promising therapeutic option in selected patients with relapsed/refractory PTCL and will change the daily clinical practice in the treatment of PTCL. However, these are not a curative option when used as a single agent. Further clinical developments are expected, comprising 1) combination therapies of new agents with cytotoxic chemotherapies; 2) ‘novel-novel’ combinations; 3) immune therapies, including chimeric antigen receptor T-cell therapy; and 4) predictive marker analysis.

Trial registration: ClinicalTrials.gov identifier: NCT00364923.

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Trial registration: ClinicalTrials.gov identifier: NCT00865969.

Trial registration: ClinicalTrials.gov identifier: NCT01777152.

Trial registration: ClinicalTrials.gov identifier: NCT01578499.

Trial registration: ClinicalTrials.gov identifier: NCT02697552.

Trial registration: ClinicalTrials.gov identifier: NCT02955589.

Trial registration: ClinicalTrials.gov identifier: NCT02953652.

Trial registration: ClinicalTrials.gov identifier: NCT01728805.

Trial registration: ClinicalTrials.gov identifier: NCT01482962.

Trial registration: ClinicalTrials.gov identifier: NCT02232516.

Trial registration: ClinicalTrials.gov identifier: NCT03593018.

Trial registration: ClinicalTrials.gov identifier: NCT01947140.

Trial registration: ClinicalTrials.gov identifier: NCT01998035.

Trial registration: ClinicalTrials.gov identifier: NCT01897012.

KEYWORDS:

• Alisertib
• azacytidine
• brentuximab vedotin
• cerdulatinib
• chidamide
• DS-3201b
• duvelisib
• forodesine
• lenalidomide
• mogamulizumab
• new agent
• pralatrexate
• PTCL
• romidepsin
• ruxolitinib
• T-cell lymphoma
• tenalisib

Article highlights

• In the past decade, several novel agents have been approved for relapsed/refractory PTCL in the US and/or other places, including Europe, China, and Japan: pralatrexate, romidepsin, brentuximab vedotin, mogamulizumab, chidamide, and forodesine.

• Development of these novel agents for PTCL has provided several useful therapeutic options for patients and have changed our daily clinical practice.

• However, there are still unmet medical needs because most patients with PTCL remain incurable. It is necessary to seek more-effective agents, combination therapies, and biomarkers that can accurately predict efficacy.

This box summarizes key points contained in the article.

Declaration of interest

K Tobinai has received research funding from Eisai, Mundipharma, Celgene, Solasia Pharma, Kyowa Hakko Kirin, and HUYA Bioscience International. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded in part by the National Cancer Center Research and Development Fund (26-A-4, 29-A-3).