EBV DNA 动态变化预测接受培门冬酶为基础治疗的早期自然杀伤/T 细胞淋巴瘤预后：来自 NHL-004 多中心随机研究的长期随访和生物标志物分析

The multi-center randomized phase III NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus the methotrexate, etoposide, dexamethasone and pegaspargase (MESA) regimen, combined with sandwiched radiotherapy, in newly diagnosed early-stage nasal natural killer / T-cell lymphoma (NKTCL).

Here we report the long-term outcomes (median follow-up, 64 months) and biomarker analysis. A total of 256 eligible patients aged 14-70 years were randomly assigned (1:1) to the ESA or the MESA arm. The 5-year progression-free survival (PFS) rates were 80. 3% and 74. 9% in the ESA and MESA arms (hazard ratio [HR]=0. 78 [95% CI: 0. 46-1. 33], P=0. 371), and the 5-year overall survival (OS) rates were 85. 1% and 80. 9% (HR=0. 74 [95% CI: 0. 40-1. 37], P=0. 332), respectively. No new safety signals related to treatments were observed. Interim plasma Epstein-Barr virus (EBV) DNA positivity and stable disease / progressive disease response were independent predictors of inferior PFS and OS.

No prognostic significance was observed according to molecular subtypes. Interim EBV DNA positivity correlated with up-regulated chromatin remodeling alterations, immune escape-related genes, and decreased infiltrating monocytes / M1 macrophages. With low toxicity, non-intravenous administration, and an outpatient design, ESA with sandwiched radiotherapy achieved long-term durable response in patients with newly diagnosed early-stage NKTCL. Dynamic monitoring of plasma EBV DNA provided a clinical rationale for future mechanism-based therapy in NKTCL.