Extranodal Natural Killer/T-Cell Lymphomas: Current Approaches and Future Directions

Abstract

Extranodal natural killer/T(NK/T)-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma that typically presents with an isolated nasal mass, but a sizeable minority present with advanced stage disease and have a significantly poorer prognosis. Those with limited disease are standardly treated with chemotherapy and radiation while those with advanced stage disease are treated with L-asparaginase containing chemotherapy regimens. The addition of modern radiation therapy techniques and the incorporation of L-asparaginase into chemotherapy regimens have significantly improved outcomes in this disease, but relapses and death from relapsed disease remain frequent. Given the high rate of relapse, several novel therapies have been evaluated for the treatment of this disease. In this review, we explore the current standard of care for ENKTL as well as novel therapies that have been evaluated for its treatment and the biologic understanding behind these therapies.

Rational Targets of Therapy in Extranodal NK/T-Cell Lymphoma

“…The cell surface protein CD30 is also expressed in the majority of ENKTL cases [119], with an unclear role as a prognostic marker [142,143]. Brentuximab vedotin (BV), a CD30directed antibody-drug conjugate that is used extensively in lymphomas, has low singleagent activity in relapsed/refractory ENKTL, with a phase II study that included 7 patients with ENKTL demonstrating an ORR of 29% (1 patient with CR) [120].…”

Epstein–Barr virus‐associated lymphomas decoded

“…CD38 and CD30 are surface proteins expressed in roughly half of cases. Daratumumab (an anti‐CD38 monoclonal antibody) and brentuximab vedotin (an anti‐CD30 antibody‐drug conjugate) have been investigated, respectively, in relapsed/refractory settings, though limited response rates were observed 124 . The role of EBV‐specific CTLs remains uncertain.…”

Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L‐asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed NK/T‐cell lymphoma: A French retrospective study

“…Extranodal NK/T-cell lymphoma (ENKTL), nasal type is a rare and aggressive disease, representing less than 1% of non-Hodgkin lymphomas (NHL) in Western populations. [1][2][3] In 60%-80% of the patients, the disease is localised to the upper aerodigestive tract. [1][2][3] Treatment of localised ENKTL was originally based on radiation therapy alone which resulted in a 80%-100% response.…”

“…[1][2][3] In 60%-80% of the patients, the disease is localised to the upper aerodigestive tract. [1][2][3] Treatment of localised ENKTL was originally based on radiation therapy alone which resulted in a 80%-100% response. While this strategy was able to control localised ENKTL, it was still associated with a high relapse rate (25%-40%) suggesting that radiotherapy alone is not sufficient to induce persistent remission in all patients.…”

“…Extranodal NK/T‐cell lymphoma (ENKTL), nasal type is a rare and aggressive disease, representing less than 1% of non‐Hodgkin lymphomas (NHL) in Western populations 1–3 . In 60%–80% of the patients, the disease is localised to the upper aerodigestive tract 1–3 .…”