Current and future management of NK/T-cell lymphoma based on clinical trials

Abstract

Recently reported results of well-designed prospective clinical trials for extranodal NK/T-cell lymphoma, nasal type (ENKL) have rapidly changed the management of ENKL. This review will focus on the evidence obtained from prospective clinical trials for ENKL and discuss the most highly recommended current management and future directions for the better management of ENKL. For patients with nasal NK/T-cell lymphoma of stage IE or contiguous stage IIE with cervical node involvement, concurrent chemoradiotherapy with radiotherapy (RT) and a two-thirds dose of DeVIC chemotherapy is recommended as a first-line treatment. To obtain the expected clinical outcome, performing RT following the same procedure as that reported is important. For the other patients with newly diagnosed ENKL, SMILE chemotherapy is recommended as an induction therapy. The Epstein-Barr virus DNA load in peripheral blood is useful for both prognostication and monitoring during the follow-up after treatment. Other L-asparaginasecontaining chemotherapies and chemotherapies containing non-multidrug resistance-related agents and etoposide are good options for elderly patients or patients with impaired organ function. As in the cases of other aggressive lymphomas, prospective clinical trials with adequate statistical considerations should be conducted to improve the prognosis of patients with ENKL.

Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma

“…L-asparaginase (L-Asp) and pegaspargase (PEGAsp) are important chemotherapeutic drugs for childhood acute lymphoblastic leukemia (ALL), and clinical trials have also shown that L-Asp treatment improves the outcome of NK/T cell lymphoma (7). The exact molecular events that cause cell death following L-Asp treatment remain unknown.…”

Dysregulation of microRNAs and their association in the pathogenesis of T-cell lymphoma/leukemias

“…(c) Extranodal PTCL (e.g., ENKL) NK/T-cell lymphoma/leukemia can be classified into leukemic and extra nodal (ENKL) types [83]. We previously showed that up-regulation of miR-21 or miR-155, and down-regulation of miR-150, occur frequently in NK/Tcell leukemia/lymphoma [44,80].…”

“…These miRNAs, respectively, regulate protein tyrosine phosphatases, Pten or Ship1, whose downregulation commonly activates AKT signaling [80]. Downregulation of miR-150 also contributes to cell proliferation and anti-aging via up-regulation of AKT2 or Dyskerin [44,83,84]. A previous review article by our group describes this in greater detail [14].…”

“…Thus, the same therapeutic strategy may be applicable in c-Mycpositive T-cell lymphoma. Indeed, miR-187 activation could stabilize c-Myc expression in PTCL-NOS and a proteasome inhibitor, bortezomib may be useful in reducing the miR-187/c-Myc axis [83]. Furthermore, it has been recently reported that c-Myc/miR-125b-5p axis determines the sensitivity of bortezomib via modulation of Maxinteracting transcriptional repressor (MAD4) in CTCL [92].…”

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T‐cell lymphoma, nasal type: a multicenter trial in Northwest China

“…The prognosis for NKTCL patients is poor, with 5‐year progression‐free survival (PFS) and overall survival (OS) rates of approximately 30% and 40%, respectively 9, 10. Historically, the poor outcome and high incidence of resistance to conventional therapy may be associated with overexpression of P‐glycoprotein, a transmembrane pump that transports anthracycline‐based chemotherapeutics and results in multidrug resistance 11, 12, 13, 14, 15.…”