NK/T Cell Lymphoma: Updates in Therapy

Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly aggressive lymphoma which used to show a poor clinical outcome. Expression of P-glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness to conventional chemotherapy containing anthracycline. However, recent innovative approaches have improved the outcome and prognosis of ENKL. The purpose of this review is to summarize the proceedings of treatment.

Concurrent chemoradiotherapy containing platinum and several drugs including L-asparaginase, methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL. SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) or other L-asparaginase-containing therapy is promising for advanced-stage ENKL, followed by either autologous or allogeneic hematopoietic stem cell transplantation. Anti-PD-1 or other immunological checkpoint inhibitors are recently reported to be effective for relapsed/refractory ENKL thought to be due to EBV-driven upregulation of PD-L1 expression. The prognosis of ENKL is therefore improving by the introduction of these strategies. The 5-year overall survival (OS) rate of limited stage was 63.2% [95% confidence interval (CI), 55.3 to 70.0%] before 2010, but was 79.4% (95% CI, 66.9 to 87.6%) in 2010 or after. However, there still exists a room for improvement, particularly for advanced-stage patients. The 2-year OS of advanced ENKL was 30.3% (95% CI, 19.5 to 41.7%) before 2010, but was 40.5% (95% CI, 24.8 to 55.8%) in 2010 or after. Optimal treatment scheme should further be explored.