Folotyn (Pralatrexate Injection) for the Treatment of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: U.S. Food and Drug Administration Drug Approval Summary

Abstract

Purpose: On September 24, 2009, the U.S. Food and Drug Administration granted accelerated approval for Folotyn (pralatrexate injection, Allos Therapeutics, Inc.) as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL); it is the first drug approved for this indication.Experimental Design: This review was based on study PDX-008, a phase II, single-arm, nonrandomized, open-label, international, multicenter trial, designed to evaluate the safety and efficacy of pralatrexate when administered concurrently with vitamin B 12 and folic acid supplementation in patients with relapsed or refractory PTCL.Results: The overall response rate was 27% in 109 evaluable patients [95% confidence interval (CI), 19-36%]. Twelve percent of 109 evaluable patients (95% CI, 7-20%)] had a response duration of ≥14 weeks. Six of these 13 patients achieved a complete response, and one patient had complete response unconfirmed. The most common grade 3 and 4 toxicities were thrombocytopenia, mucositis, and neutropenia.Conclusion: This accelerated approval was based on a response rate that is reasonably likely to predict clinical benefit in this heavily pretreated patient population with this rare disease. The applicant has committed to conducting postmarketing clinical trials to assess clinical benefit. The recommended starting dose of pralatrexate in patients with relapsed or refractory PTCL is 30 mg/m 2 via intravenous push over 3 to 5 min weekly for 6 weeks followed by a one-week rest (one cycle). Intramuscular injection of 1 mg vitamin B 12 should be administered every 8 to 10 weeks along with 1.0 mg folic acid given orally once a day. Clin Cancer Res; 16(20); 4921-7. ©2010 AACR.

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma

“…17p4124 Pralatrexate, a folate analog, received accelerated approval by the FDA in 2009 for relapsed PTCL, representing the only FDA approved therapy for this disease. 32 In 109 patients enrolled on a phase 2 study, the overall response rate for patients with PTCL was 27%, with 7 patients in CR. The median duration of response was 9.4 months.…”

A Review of Autologous Stem Cell Transplantation in Lymphoma

“…Four additional drugs are now approved in the US to treat R/R PTCL and these include pralatrexate, romidepsin, belinostat, and BV. Response rates with pralatrexate, romidepsin, and belinostat range from 25 to 54% in mixed R/R PTCL populations [87], while 86% of ALCL patients respond to BV [88]. Extranodal NK/T-cell lymphoma, nasal type (ENKL) is associated with Epstein-Barr virus (EBV) and have poor prognosis.…”

The impact of 5-formyltetrahydrofolate on the anti-tumor activity of pralatrexate, as compared to methotrexate, in HeLa cells in vitro

“…However, pralatrexate can be administered parenterally at a weekly dose of 30 mg/m 2 with folic acid supplementation, comparable to the weekly dosing for MTX [10,5]. Based upon the relative potencies of pralatrexate and MTX, current pralatrexate regimens might be considered comparable to “high-dose” MTX without leucovorin (6(R,S)5-formylTHF) “rescue”.…”