Introduction: Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T-cell lymphoma characterized by a poor prognosis. Treatments are associated with high rates of relapse, and thus there exists an unmet medical need for new, improved therapies. Mogamulizumab is a novel defucosylated monoclonal antibody targeting C-C chemokine receptor 4 that eradicates malignant cells via antibody-dependent cellular cytotoxicity (ADCC).
Areas covered: Phase I-III clinical trials involving mogamulizumab demonstrated its significant efficacy and tolerability. In the phase III MAVORIC study, mogamulizumab exhibited greater efficacy than vorinostat (response rate, 28% versus 5%; median progression-free survival, 7.7 versus 3.1 months, respectively) for advanced, relapsed/refractory MF/SS. Responses were durable (median, 14.1 months), and response rates were highest in SS (37%) and within the blood compartment (68%). Common adverse events include infusion reactions and drug eruptions. The drug also increases the risk of immune-mediated complications such as autoimmune disease and acute graft-versus-host disease following transplantation.
Expert opinion: Mogamulizumab represents a valuable therapy for advanced MF/SS as it can produce prolonged responses, particularly within the peripheral blood. Since it eliminates malignant T cells via ADCC, combining mogamulizumab with immunotherapeutic agents such as interferons, interleukin-12, and Toll-like receptor agonists may further enhance its efficacy.
Keywords: C–C chemokine receptor 4; Mogamulizumab; Sézary syndrome; antibody-dependent cellular cytotoxicity; cutaneous T-cell lymphoma; mycosis fungoides; natural killer cells; regulatory T cells.