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Overview of the current treatment strategy in extranodal NK/T-cell lymphoma: from diagnosis to recurrence

Extranodal natural killer/T cell lymphoma (ENKTL) is an extraordinary subtype of nonHodgkin’s lymphoma (NHL), mainly involves the nasal cavity and the upper airway, and is influenced by the Epstein-Barr virus (EBV). Compared to other subtypes of T-cell lymphoma, ENKTL cannot be effectively treated with commonly used anthracycline-based systemic chemotherapy. Thus, the recent treatment of ENKTL has undergone significant changes based as informed by various clinical trials and prospective studies. Concurrent, sequential, and sandwich chemoradiotherapy, which is based on the alteration of the order of radiation and chemotherapy, has emerged as vital treatment approach for localized ENTKL. After the emergence of anthracycline-based systemic chemotherapy, nonanthracycline-based chemotherapy combined with L-asparaginase, including SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide), Asp-MTX-Dex (L-asparaginase, methotrexate and dexamethasone), and DDGP (dexamethasone, cisplatin, gemcitabine, and peg-asparaginase) has attracted attention in advanced and relapsed/refractory (R/R) ENKTL treatment. Moreover, autologous-stem cell transplantation (auto-SCT) or allogenic stem cell transplantation (allo-SCT) has been recommended as a treatment option when patients with advanced or relapsed ENKTL achieve remission by a salvage treatment strategy. Even if ENKTL recurs, the effectiveness of immune checkpoint inhibitors (ICIs) related to programmed death-ligand 1 (PDL1) has been proven, which is representative of the broadening of treatment options compared to many years ago. However, despite the marked improvement of therapeutic strategies in ENKTL, some patients still have dismal outcomes. Based on the understanding of the molecular and immunologic biology of ENKTL, the treatment strategy and treatment prognostic prediction model of ENKTL has been continuously evolving, treatment experience has been gradually enriched, and related data has accumulated. In this review, we discuss the current and emerging treatments for early or advanced relapsed or refractory ENKTL.