Adult T-Cell Leukemia-Lymphoma.

Abstract

Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-lymphocyte malignancy caused by an RNA retrovirus, human T-cell leukemia virus type 1. ATL is clinically classified into four disease subtypes. The acute, lymphoma type, and cases of the chronic type involving unfavorable prognostic factors are regarded as aggressive ATL subtypes that require immediate treatment. Dose-intensified chemotherapy, such as the VCAP-AMP-VECP regimen, is considered to be the most recommended treatment for aggressive ATL. However, ATL remains difficult to cure and has an extremely poor prognosis, even when such chemotherapy is employed. Allogeneic stem cell transplantation is the only known curative therapy and is recommended for younger patients with aggressive ATL. However, because of the increasing age at the onset of ATL, only a small fraction of patients with ATL can benefit from such transplants; therefore, there is an unmet medical need for novel drugs. Mogamulizumab, a defucosylated, humanized anti-C-C motif chemokine receptor 4 (CCR4) monoclonal antibody, was developed using a novel glycoengineering technique. Mogamulizumab monotherapy achieved clinically meaningful effects in patients with relapsed aggressive ATL and has exhibited acceptable toxicity profiles both inside and outside of Japan. In addition, lenalidomide has shown promising antitumor activity in patients with ATL. Furthermore, based on the results of translational research, several promising novel agents are currently being investigated and might contribute to improving the prognosis of ATL.