Department of Experimental Pathology, Microbiology, and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon;
Inserm UMR1163 & CNRS URL 8254,
Institut Imagine, Paris, France;
Department of Hematology, Necker-Enfants Malades Hospital, University of Paris-Descartes, AP-HP, Paris, France;
Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon;
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Adult T-cell leukaemia/lymphoma (ATL) is an aggressive tumour secondary to chronic infection by HTLV-I retrovirus. ATL is classified into four clinical forms (acute, lymphomatous, chronic, and subacute or smouldering). Antiretroviral therapy combining zidovudine (AZT) and interferon alpha (IFNα) significantly prolongs the survival of patients with indolent forms (chronic and subacute) compared to the “watch and wait” strategy without treatment or conventional chemotherapy. Regarding the aggressive forms (acute and lymphomatous), several clinical trials have shown that patients with ATL lymphoma, but not acute ATL, may benefit from the chemotherapy combinations used for aggressive lymphoma. Patients with ATL lymphoma may also benefit from induction chemotherapy, in combination or sequentially, with AZT/IFNα-based antiviral therapy. Acute ATL has a very poor prognosis due to drug resistance and immune deficiency. AZT/IFNα provides long-term disease control in approximately 25–30% of patients with acute ATL, especially those who achieve complete remission and those without p53 mutation. Prophylaxis of meningeal relapse and opportunistic infections is essential in the management of these patients. Allogeneic haematopoietic stem cell transplantation provides long-term control for about a third of transplant patients. Unfortunately, only a small percentage of patients receive allotransplantation. The prognosis for refractory or relapsing patients remains appalling, although encouraging results have been obtained using lenalidomide or mogamulizumab. To overcome the problems of chemotherapy resistance and to prevent relapses, new therapeutic avenues based on preclinical and clinical studies of targeted treatments are being explored. These include, for example, arsenic trioxide, new monoclonal antibodies and therapies targeting epigenetic changes. Anti-ATL vaccines, using dendritic cells activated by peptides specific for the viral oncoprotein Tax, have elicited interesting immune and clinical responses. Finally, these new therapeutic approaches adapted to the different clinical forms of ATL must also take into account the host's immune response and micro-environment, including non-malignant cells infected with HTLV-1 virus. This review presents a general overview of preclinical or clinical studies exploring new therapeutic avenues for ATL.