T-cell lymphomas (TCL) are a diverse and heterogeneous group of
malignancies that represent less than 15% of all non-Hodgkin
lymphomas. Initial refinements of the clinical classification of these complex diseases have been made, but a better understanding of their molecular pathogenesis is still needed. Even if the paucity of insights into the underlying pathogenesis of TCLs has hindered our ability to develop rational targeted
therapies, significant advances have been made.
Pralatrexate (10-propargyl 10-deazaaminopterin) is a unique
antifolate that has been rationally designed to have high affinity for the reduced
folate receptor (RFC) and the
folylpolyglutamate synthetase (FPGS) and was the first
drug ever approved for the treatment of relapsed and refractory
peripheral T-cell lymphomas (PTCL). This review describes the preclinical development of
pralatrexate that led to early-phase clinical trials in
lung cancer and
lymphoma and its subsequent approval in PTCL. The review also describes how
pralatrexate has been combined with other agents in both the preclinical and clinical settings. FDA approval for the use of
pralatrexate in PTCL has been granted based on the results of the pivotal Phase II trial of this agent in relapsed and refractory PTCL patients. clinical development,
pralatrexate, preclinical data,
T-cell lymphoma.