Bridging therapy with valemetostat to allogeneic hematopoietic cell transplantation for adult T-cell leukemia/lymphoma

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus-1. Patients diagnosed with aggressive ATL have a poor prognosis. As response duration to conventional multiagent chemotherapy is short, upfront allogeneic hematopoietic cell transplantation (allo-HCT) is recommended. As disease status at the time of allo-HCT is the primary prognostic factor, bridging therapy to allo-HCT is sometimes necessary during donor coordination. However, conventional chemotherapies are often toxic, particularly for older patients and those with inadequate hematopoietic recovery. Anti-CCR4 monoclonal antibody mogamulizumab adversely affects post-transplant survival due to the high risk of severe graft-versus-host disease (GVHD). Available data on other novel agents for ATL are limited. The present case study details an ATL patient who exhibited chemotherapy intolerance, but was successfully bridged to unrelated peripheral blood stem cell transplantation (uPBSCT) with valemetostat, a selective dual inhibitor of enhancer of zeste homolog 1 and 2. Despite severe bone marrow failure, valemetostat was well tolerated by the patient and led to successful disease control prior to uPBSCT, which is considered to have contributed to a reduced risk of post-transplant relapse and an improved prognosis. No significant adverse effects of valemetostat were observed early after transplantation, in contrast to the increased incidence of severe GVHD and non-relapse mortality reported following allo-HCT after mogamulizumab therapy. These findings suggest that valemetostat is a promising option as a bridging therapy to allo-HCT for aggressive ATL.