Development of new agents for peripheral T-cell lymphoma

Abstract

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. Trial registration: ClinicalTrials.gov identifier: NCT01796002. 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.