Novel therapies for peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a diverse family of lymphoid neoplasms with poor prognosis. They represent approximately 6-10% of non-Hodgkin lymphomas with significant geographic variation. The median age at diagnosis varies with histology, however the majority of patients with PTCL are in their fifth or sixth decade of life. Until recently clinical development of new agents for PTCL was slow due to difficulties in making the correct diagnosis, lack of uniform classification and combination of rarity and biologic diversity of the group. In the last 5 years, significant advances were made to overcome these obstacles, leading to the approval of three new agents for relapsed and refractory PTCL by the Food and Drug Administration, based on well conducted prospective studies. Pralatrexate, a unique antifol, was the first agent granted approval, followed by romidepsin, a histone deacetylase inhibitor, and brentuximab vedotin, an immunoconjugate. Owing to the unique nature of these agents, durable responses were seen in patients with highly refractory disease, and some of these responses are long lasting after discontinuation of therapy. Accumulating data indicate that these novel agents have little cumulative toxicity and can be administered continuously to patients who are not candidates for consolidative stem-cell transplantation (SCT), with little impact on quality of life. They might also provide a new salvage option for patients eligible for SCT with no impact on autologous stem-cell collection or subsequent engraftment. New studies are underway to evaluate efficacy and safety of new agents in combination regimens for both newly diagnosed and relapsed/refractory PTCL. Several other investigational drugs showed promise in recent trials. This review focuses on novel therapies for T-cell lymphomas, their place in current treatment paradigms and future directions.