Pralatrexate: an emerging new agent with activity in T-cell lymphomas.
OBJECTIVE
T-cell lymphomas (TCL) represent a particularly poor prognosis subgroup of lymphomas. The goal of this review is to provide emerging information on one agent demonstrating activity in these challenging diseases. Pralatrexate is a novel antifolate designed to have high affinity for the reduced folate carrier type 1 (RFC-1). Preclinical and clinical studies have demonstrated that pralatrexate has significant activity against TCL.


RESULTS
The high affinity of pralatrexate for RFC-1 significantly improves its internalization into cells. Preclinical studies in models of B-cell lymphomas and TCL have demonstrated that pralatrexate demonstrates activity superior to traditional antifolates. Phase I studies have shown the dose-limiting toxicity to be stomatitis, which can be abrogated with folic acid and vitamin B12 supplementation. Early phase studies have shown marked activity across a diverse panoply of TCL.


CONCLUSIONS
Pralatrexate is an antifolate designed to be internalized more rapidly than other traditional antifolates. Preclinical studies have demonstrated its superiority to methotrexate, and early phase I and II studies have shown marked activity across many poor-risk subtypes of TCL. Future studies are directed towards understanding the pharmacokinetic features of the drug, and expanding the population of patients with TCL and B-cell lymphomas.
O'Connor
Owen A
OA
Laboratory of Experimental Therapeutics for Lymphoproliferative Malignancies, Department of Medicine, Division of Hematologic Malignancies, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York 10021, USA. oconnoro@mskcc.org
D000630:Aminopterin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy*
C418863:10-propargyl-10-deazaaminopterin; D005493:Folic Acid Antagonists; D000630:Aminopterin