[Treatment of adult T-cell leukemia/lymphoma: past, present, and future]

Adult T-cell leukemia/lymphoma (ATL) is a T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1). Treatment strategies have been established by classification of ATL as aggressive (acute, lymphoma, and chronic ATL with any unfavorable prognostic factors) or indolent (smoldering and chronic ATL without any unfavorable prognostic factors). The standard of care (SOC) for aggressive ATL has been dose-intensified multi-agent chemotherapy. The introduction of allogeneic hematopoietic stem cell transplantation was a treatment breakthrough for patients around 70 years or younger. Moreover, five novel drugs have been approved and entered clinical use in Japan since 2012. Outside Japan, the combination of interferon-alfa and zidovudine (IFN/AZT) has been considered a SOC, despite a lack of well-designed clinical trials. The SOC for indolent ATL is watchful waiting in Japan, but also includes IFN/AZT for symptomatic cases outside Japan. In the absence of robust evidence for either approach, a phase 3 trial to validate the benefit of IFN/AZT is ongoing in Japan, and the results are due to be published in late 2025. Looking to the future, there is an obvious decline in HTLV-1 infected individuals in the younger population in Japan, and the success of a nationwide program preventing mother-to-child infection by recommending avoidance of breastfeeding should further contribute to this trend.