WS3-4 - New Treatment Modalities for Atl

Abstract

ATL is a distinct malignancy of Treg/TH2 cells with caused by HTLV-1. ATL still has a worse prognosis than other T-cell malignancies in general. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into acute, lymphoma, chronic, and smoldering types. In case acute, lymphoma or unfavorable chronic subtypes (aggressive ATL), and favorable chronic or smoldering subtypes (indolent ATL), intensive chemotherapy followed by allogeneic stem cell transplantation and watchful waiting until disease progression has been recommended, respectively in Japan. A retrospective analysis suggested that the combination of interferon alpha and zidovudine was promising for the treatment of ATL, especially for leukemic subtypes. There is no plateau with an initial steep slope and subsequent gentle slope in the survival curves for aggressive and indolent ATL treated with chemotherapy and watchful waiting, respectively, although the prognosis is much better in the latter (MST; 1 year vs. 5 years), suggesting the need of refinement of subtype-classification. Defucosylated humanized anti-CCR4 monoclonal antibody (mogamulizumab), which showed strengthened ADCC activity as compared to usual Ab in preclinical analysis, was approved for the treatment of relapsed/refractory ATL based on the results of phase I and II studies, with response rate of about 50% and manageable toxicities including moderate to severe skin reaction, in Japan. Recently, the results of the subsequent randomized phase II study of chemotherapy +/- mogamulizumab for untreated patients with aggressive ATL was reported. This combination is anticipated because the former was more effective for ATL cells in lymphnode than those in peripheral blood and the latter was vice versa. The combination of mLSG15 plus mogamulizumab was well tolerated and produced a higher CR rate. Several new agent trials for ATL are ongoing and in preparation after translational research, including histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor and lenalidomide.