Emerging therapeutic strategies for mature T-cell and natural killer-cell lymphomas

Mature T-cell and natural killer-cell neoplasms are a heterogenous group of uncommon lymphomas. Conventional therapy with mainly cytotoxic chemotherapy for this subgroup is suboptimal, and the treatment outcome is unsatisfactory. With the advances in the understanding of disease biology, considerable progress has been made in recent years. Monoclonal antibodies or antibody-drug conjugates targeting T-cell lymphoma surface antigens have been approved, including brentuximab vedotin, for the treatment of CD30-positive nodal and cutaneous T-cell lymphoma, and mogamulizumab, for mycosis fungoides and adult T-cell leukaemia/lymphoma. Furthermore, immune checkpoint blockade has also shown promise in the management of mycosis fungoides and extranodal natural killer/T-cell lymphoma. Epigenetic dysregulation is frequently found in mature T-cell and natural killer-cell lymphomas; hence, therapeutic agents acting on epigenetic regulators, such as histone deacetylase inhibitors, have been tested in clinical trials with promising results. Novel approaches including cell therapy and adoptive immunotherapy are currently being evaluated. In this Series paper, we discuss the limitations of the conventional treatment options and the use of these novel approaches for mature T-cell and natural killer-cell lymphomas.