Pralatrexate, a novel class of antifol with high affinity for the reduced folate carrier‐type 1, produces marked complete and durable remissions in a diversity of chemotherapy refractory cases of T‐cell lymphoma

Abstract

Pralatrexate, a novel class of antifol with high affinity for the reduced folate carrier-type 1, produces marked complete and durable remissions in a diversity of chemotherapy refractory cases of T-cell lymphoma Based on the most recent surveillance epidemiology and end results registry data (Morton et al, 2005), it is estimated that there are 114 548 cases of lymphoid neoplasms per year in the United States, of which 87 666 (about 76%) are B-cell lymphoid neoplasms and 10 042 are Hodgkin lymphoma. Only 5-6% of lymphoid malignancies (6228 cases per year) are T/natural killer (NK) cell neoplasms. A series of other studies have found T-cell lymphomas (TCLs) to constitute a small fraction of total non-Hodgkin lymphomas (NHLs) in the US, with reports typically ranging from 10 to 15% (Devesa & Fears, 1992) In general, TCLs carry a worse prognosis than B-cell lymphomas. In a retrospective analysis of sequential Groupe d'Etudes des Lymphomes de l'Adulte trials for aggressive lymphomas (Gisselbrecht et al, 1998), the 5-year survival rate for patients with 1, 2 or 3 risk factors with B-versus TCL was 63% vs. 60%, 53% vs. 36% and 35% vs. 23% respectively. Similar adverse results for TCL were also observed for the rate of complete remission (CR). Furthermore, the International Lymphoma Study Group classification project found that peripheral TCL (PTCL) and precursor T-lymphoblastic leukaemia/lymphoma (T-ALL) had some of the worst outcomes of any subtype of lymphoma, with a 5-year survival rate of 26% following treatment with standard doxorubicin containing regimens (Rudiger et al, 2002). There are indolent subtypes of TCL, such as mycosis fungoides and primary cutaneous anaplastic large cell lymphoma (ALCL), which do not follow this universally poor prognosis. Among the aggressive TCLs,

Treatment of Adult T-cell Leukemia

“…121 All four patients with T-cell lymphoma including one ATL patient of 20 lymphoma patients in this study achieved a CR. In other study, 14 (54%) of 26 patients with T-cell lymphoma showed CR (8 patients) and PR (6 patients).…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Pralatrexate, a novel antifolate with a high affinity for the reduced folate carrier (RFC-1) and novel mechanism of resistance when compared with methotrexate [357][358][359], was associated with an overall response rate of 29% in the PROPEL study, which was comprised largely of peripheral T-cell lymphoma patients, the majority of which had disease refractory to the most recent treatment [360]. Twelve patients with transformed MF were included in the study [361].…”

Novel therapeutic agents for B-cell lymphoma: developing rational combinations

“…Pralatrexate was studied in a phase 1/2 trial by O'Connor et al 77 where 20 patients with relapsed/refractory non-Hodgkin and Hodgkin lymphoma were treated. The MTD was determined to be 30 m/m 2 every week for 6 of 7 weeks.…”