CHOP Plus Sequential Mogamulizumab As First-Line Therapy for Untreated Adult T-Cell Leukemia-Lymphoma

Introduction: Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. In younger patients, allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to improve prognosis through a graft-versus-ATL (GvATL) effect. On the other hand, elderly patients with ATL are often not amenable to HSCT, and the prognosis is extremely poor with existing chemotherapy. The most widely used chemotherapy for ATL, CHOP (combination of cyclophosphamide-doxorubicin-vincristine-prednisone) and similar chemotherapy, have shown a complete response (CR) rate of about 20% and a long-term prognosis of less than 10%. In a phase II study of mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, in concurrent combination with chemotherapy (mLSG15), the primary endpoint of CR was 52% in the mLSG15 + mogamulizumab group compared to 33% in the mLSG15 alone group. However, no improvement was observed in overall survival (OS) or progression-free survival (PFS). In addition, mLSG15 is a potent chemotherapy and not feasible in majority of elderly patients. Considering the possibility that mogamulizumab may unlock the tumor immune evasion mechanism by removing regulatory T cells and exert an immunological effect like GvATL, we investigated its usefulness as an immunological consolidation therapy following chemotherapy, with the aim of suppressing recurrence.