Durable response to pralatrexate for aggressive PTCL subtypes

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature Tand natural killer-cell neoplasms that comprise about 10%-15% of all non-Hodgkin lymphomas in the United States.1,2 The development of effective therapies for PTCL has been challenging because of the rare nature and heterogeneity of these lymphomas. Most therapies are a derivative of aggressive B-cell lymphoma therapies, including CHOP (cyclophosphamide, hydroxydaunorubicin, vinicristine, prednisone) and CHOEP (cyclophosphamide, hydroxydaunorubicin, vinicristine, etoposide, prednisone).1 Many centers use autologous or allogeneic stem cell transplant in this setting,1 but outcomes remain poor and progress in developing effective treatments has been slow. Pralatrexate is the first drug to have been approved by the US Food and Drug Administration specifically for treating patients with relapsed or refractory PTCL.3 As a folate analog metabolic inhibitor, pralatrexate competitively inhibits dihydrofolate reductase and reduces cellular levels of thymidine monophosphate, which prevents the cell from synthesizing genetic material and triggers it to undergo apoptosis.4 The agency’s approval of pralatrexate was based on results from the PROPEL study, which is possibly the largest prospective study conducted in patients with relapsed or refractory PTCL (109 evaluable patients).2 Findings from the study showed an overall response rate (ORR) of 29%, and a median duration of response (DoR) of 10 months.2 Pralatrexate is administered intravenously at 30 mg/m2 once weekly for 6 weeks of a 7-week treatment cycle. It is generally continued until disease progression or an unacceptable level of toxicity.2 Alternative dosing schedules have been described, including 15 mg/m2 once weekly for 3 weeks of a 4-week treatment cycle for cutaneous T-cell lymphomas.5 In this case series, we examine the outcomes of 2 patients with particularly aggressive subtypes of PTCL who were treated with pralatrexate. The significance of this report is in describing the long duration of response and reporting on a PTCL subtype – subcutaneous panniculitis-like T-cell lymphoma, alpha/beta type – that was underrepresented in the PROPEL study and is underreported in the literature.