Changing the Paradigms of Treatment in Peripheral T-cell Lymphoma: From Biology to Clinical Practice

Abstract

Despite enormous advances in our understanding of aggressive lymphomas, it is clear that progress in the peripheral T-cell lymphomas (PTCL) has lagged well behind other B-cell malignancies. Although there are many reasons for this, the one commonly cited notes that the paradigms for diffuse large B-cell lymphoma (DLBCL) were merely applied to all patients with PTCL, the classic "one-size-fits-all" approach. Despite these challenges, progress is being made. Recently, the FDA has approved four drugs for patients with relapsed/refractory PTCL over the past 5 years, and if one counts the recent Japanese approval of the anti-CCR4 monoclonal antibody for patients with adult T-cell leukemia/ lymphoma, five drugs have been approved worldwide. These efforts have led to the initiation of no fewer than four randomized clinical studies exploring the integration of these new agents into standard CHOP (cyclophosphamide-Adriamycin-vincristine-prednisone)-based chemotherapy regimens for patients with newly diagnosed PTCL. In addition, a new wave of studies are exploring the merits of novel drug combinations in the disease, an effort to build on the obvious single-agent successes. What has emerged most recently is the recognition that the PTCL may be a disease-characterized by epigenetic dysregulation, which may help explain its sensitivity to histone deacetylase (HDAC) inhibitors, and open the door for even more creative combination approaches. Nonetheless, advances made over a relatively short period of time are changing how we now view these diseases and, hopefully, have poised us to finally improve its prognosis.

Belinostat in patients with refractory or relapsed peripheral T-cell lymphoma: a perspective review

“…The degree of histone acetylation affects the balance between euchromatin and heterochromatin, which directly affects transcriptional activation. While the steps involved in lymphomagenesis are a complex multistep process, dysregulation of the HAT-HDAC balance has been well established as a significant event in this process, and provides a rationale for utilizing HDAC inhibitors in PTCL [Glozak et al 2005;O'Connor et al 2014]. A total of 18 different HDACs are described, belonging to 4 different classes which can be further differentiated by their zinc dependency.…”

Human T-cell Lymphotropic Virus Type I–Associated Adult T-cell Leukemia–Lymphoma: New Directions in Clinical Research

“…Furthermore, as described in more detail in the CCR Focus article by O'Connor and colleagues (77), more than 10 promising new agents for PTCL/CTCL, including ATL, are undergoing clinical trials or are in preparation with translational research. Future clinical trials on ATL should be carefully and appropriately conducted to ensure that the international consensus on ATL management is continually updated to establish evidence-based practical guidelines.…”

Are We Nearing an Era of Chemotherapy-Free Management of Indolent Lymphoma?

“…A brief overview of such treatments is presented in this review, whereas new directions in other lymphoma subtypes are presented in this edition of CCR Focus (83)(84)(85)(86)(87). Among other promising approaches, combining anti-CD20 antibodies with IMiDs, mAbs directed against other surface antigens such as CD22, immunomodulatory antibodies such as PD-1, or inhibitors of the B-cell receptor (BCR) pathway is of paramount interest.…”