Investigational drugs for T-cell lymphoma

ABSTRACT

Introduction: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of malignancies frequently associated with a poor outcome. The frontline treatment strategy for PTCL relies mostly on CHOP or CHOP-like regimens, which are associated with a high failure rate and frequent relapses.

Areas covered: In this review, the authors present recently registered drugs and their positioning in the therapeutic armamentarium against PTCL and new drugs currently in development. The successful results in CD30-positive anaplastic large cell lymphomas suggest that a better characterization of these lymphomas could open new areas of efficient drug development.

Expert opinion: Advances in the field of molecular biology have started to unravel the anomalies associated with T-cell malignancies. Recent knowledge on potential epigenetic modifiers like IDH2, which is frequently mutated in angioimmunoblastic T-cell lymphoma, opens new areas of research and confirms that epigenetic drugs could represent an attractive area of clinical research. The recently developed immune checkpoints regulators might represent another area of potential interest.

KEYWORDS:

• Chemotherapy
• epigenetics
• immune check points
• PTCL

Financial and competing interests disclosure

V Ribrag has acted as an advisory board member for Gilead Sciences, Celgene, Servier, PharmaMar and Epizyme. He also received research funding from Bayer Healthcare, Eisai Co., Ltd and Servier. 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 apart from those disclosed.

Article highlights.

• T-cell lymphomas represent a heterogeneous group of hematological malignancies usually characterized by an aggressive behavior and a very poor prognosis, except in the anaplastic large cell lymphoma subtype.

• Frontline treatment strategy relies mostly on CHOP or CHOP-like regimens, which are associated with a high failure rate and frequent relapses. The impact of high dose consolidation therapy with autologous or allogeneic stem cell transplantation either in frontline or after a relapse remains unclear because of the lack of controlled studies and conflicting results.

• As opposed to B-cell lymphomas, the prognosis of T-cell lymphomas remains poor, suggesting that molecules with different mechanisms of action are required to compensate for the mediocre efficacy of conventional cytotoxic agents.

• At present, most trials with new drugs either in monotherapy or in combination with CHOP-like regimens have failed to demonstrate a clear benefit in terms of survival.

• Research is ongoing on several drugs with various mechanisms of action (monoclonal antibodies, histone deacetylase inhibitors, kinase inhibitors, IMIDs, immune checkpoint regulators). In most of cases, they usually do not target oncogenic events in T-cell lymphomas.

• The biology of T cell lymphomas has remained poorly understood for a long time, but recent advances in the field of molecular biology have allowed the identification of recurrent mutations and/or dysregulation of cellular pathways that may constitute the basis for targeted therapy.

• In relapsed anaplastic large cell lymphoma, the clinical validity of a targeted approach has been demonstrated with crizotinib, a small inhibitor of the anaplastic lymphoma kinase, and brentuximab vedotin, a coupled monoclonal antibody against CD30.

This box summarizes key points contained in the article.