The potential of pralatrexate as a treatment of peripheral T-cell lymphoma

Expert Opin Investig Drugs. 2014 May;23(5):711-8. doi: 10.1517/13543784.2014.902050. Epub 2014 Mar 25.

Abstract

Introduction: Peripheral T-cell lymphomas (PTCLs) are a group of rare malignancies originating from clonal proliferation of mature, post-thymic T cells that represent 10 - 15% of all non-Hodgkin's lymphomas with poor prognosis and median survival of 1 - 3 years. The standard treatment for PTCL has not yet been identified. Many patients with PTCL are refractory to first-line therapy. The complete response rate ranges from 36 to 66% according to different PTCL subtypes. Furthermore, those who reached a complete or partial response often have a shorter progression-free survival.

Areas covered: This paper discusses the potential of pralatrexate , a methotrexate analogue, as a treatment of PTCL. The authors report on the efficacy and safety data of controlled studies and describe the end points of ongoing trials. Pralatrexate was the first drug to obtain FDA approval for the treatment of patients with relapsed or refractory PTCL. However, the European Medicines Agency has refused marketing authorization.

Expert opinion: None of the treatments commonly used today have given satisfactory results. Pralatrexate seems to be one of the most promising agents in the treatment of patients with PTCL. Future efforts should be focused on better understanding the molecular pathogenesis of PTCL and on specific trials for different PTCL subtypes using rational drug combinations that include pralatrexate.

Publication types

  • Review

MeSH terms

  • Aminopterin / analogs & derivatives*
  • Aminopterin / pharmacokinetics
  • Aminopterin / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic / trends
  • Folic Acid Antagonists / pharmacokinetics
  • Folic Acid Antagonists / therapeutic use*
  • Humans
  • Lymphoma, T-Cell, Peripheral / diagnosis
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / metabolism
  • Treatment Outcome

Substances

  • 10-propargyl-10-deazaaminopterin
  • Antineoplastic Agents
  • Folic Acid Antagonists
  • Aminopterin