New directions in treating peripheral T-cell lymphomas (PTCL): leveraging epigenetic modifiers alone and in combination

Abstract

The peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas originating from mature T- and NK-cells. They are aggressive diseases often resistant to chemotherapy. Areas Covered: The methodology of this review involves a literature search of data published on PubMed, abstracts from international conferences, and our own research. Recent evidence suggests that PTCL are 'epigenetic' driven diseases, an observation underscored by a series of clinical and biological observations. First, recurring mutations in genes that drive genome methylation are commonly seen across the major subtypes of the disease. Second, murine models predicated on TET2 deletions produce follicular T-helper cell subtypes of PTCL, including angioimmunoblastic T-cell lymphoma, underscoring the driver role of these epigenetic lesions in the pathogenesis of the disease. Finally, histone deacetylase inhibitors have unique activity in PTCL with four approved globally for patients with relapsed/refractory PTCL. Collectively, these findings support a fundamental role for targeting this underlying biology as a potential new direction in the development of novel platforms for the disease. Expert Opinion: In this review, we discuss the spectrum of novel therapies in PTCL, with a specific focus on epigenetic approaches, and how we aim to develop new strategies in PTCL care.

Keywords: Peripheral T-cell lymphomas; epigenetic modifiers; histone deacetylase inhibitors; hypomethylating agents.