Aggressive
T cell lymphomas are a subgroup of
lymphomas with a particularly poor prognosis. This is especially true for patients with recurrent or refractory disease, who typically have limited response to
salvage therapy and extremely poor overall survival. For this reason, there is a strong need to develop potentially active drugs for these
malignancies.
Pralatrexate is a novel
antifolate designed to have high affinity for
reduced folate carrier type 1. Preclinical and clinical studies have demonstrated that
pralatrexate has significant activity against
T cell lymphomas. The dose-limiting toxicity for
pralatrexate is
mucositis, which can be abrogated with
folic acid and
vitamin B12 supplementation.
Pralatrexate is the first single agent approved for the treatment of patients with relapsed or refractory
peripheral T cell lymphoma. This approval was based on an overall objective response rate observed in the pivotal study. The overall response rate was 29%, with a median duration of 10.1 months. This article reviews the biochemistry, preclinical experience, metabolism, and pharmacokinetics of
pralatrexate, including the clinical experience with this agent in
lymphoma. Future areas of development are now focused on identifying synergistic combinations of
pralatrexate with other agents and the evaluation of predictive markers for clinical benefit.