Mechanisms and interventions in relapsed/refractory extranodal natural killer/T-cell lymphoma

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin's lymphoma associated with Epstein-Barr virus and typically involves extranodal sites. The traditional CHOP regimen is no longer standard owing to drug resistance, whereas asparaginase-based therapies have become the mainstay of treatment. However, resistance and tumor invasion lead to relapses in 40-50% of patients, with 20% progressing to relapsed/refractory ENKTL, resulting in a median survival of <12 months. Management of ENKTL remains challenging, with an unmet clinical need. However, although the prognosis for relapsed/refractory ENKTL is poor, the development of new treatment strategies is progressing with a better understanding of the disease. This review examines factors contributing to treatment resistance, underlying resistance mechanisms and potential strategies to overcome ENKTL resistance.