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New molecular entity: Pralatrexate injection (Folotyn) was approved on September 24, 2009, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma.
Pralatrexate is a folate analogue metabolic inhibitor that competitively inhibits dihydrofolate reductase, a folic acid-dependent enzyme involved in the building of nucleic acids and other cellular processes. Pralatrexate was approved on September 24, 2009, under FDA's accelerated approval process allowing earlier approval of drugs for unmet medical needs, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
Efficacy. To evaluate pralatrexate in the treatment of relapsed or refractory PTCL, researchers conducted a phase 2, open-label, single-arm, multicenter, international clinical trial in 115 patients with relapsed or refractory PTCL. Of these enrolled patients, 111 received intravenous pralatrexate in addition to vitamin B12 and folic acid supplementation and 109 patients were evaluable for efficacy, which was the primary end point and the basis for FDA approval: 27% of patients (29 out of 109) experienced a complete or partial response to treatment, 8% of patients (9 out of 109) had a complete response, 18% of patients (20 out of 109) had a partial response.
Safety. The safety of pralatrexate was evaluated in the 111 PTCL patients who received a starting dose of 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The median duration of treatment was 70 days (range, 1-540 days). Treatment was discontinued in 25 patients (23%) due to adverse reactions. The most common adverse reactions observed in patients with relapsed or refractory PTCL with pralatrexate were mucositis, thrombocytopenia, nausea, and fatigue. Forty-four percent of patients (49 out of 111) experienced a serious adverse event while on study or within 30 days after their last dose of pralatrexate. The most common serious adverse events (>3%), regardless of causality, were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. Twenty-three percent of patients (25 out of 111) discontinued treatment with pralatrexate because of adverse reactions.
Patients must be supplemented with vitamin B12, 1 mg IM every 8 to 10 weeks, and folic acid 1.0 to 1.25 mg orally each day.