Dynamic change in Epstein-Barr virus DNA predicts prognosis in early stage natural killer/T-cell lymphoma with pegaspargase-based treatment: long-term follow-up and biomarker analysis from the NHL-004 multicenter randomized study

Dynamic change in Epstein-Barr virus DNA predicts prognosis in early stage natural killer/T-cell lymphoma with pegaspargase-based treatment: long-term follow-up and biomarker analysis from the NHL-004 multicenter randomized study

The multi-center randomized phase 3 NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus methotrexate, etoposide, dexamethasone and pegaspargase (MESA) regimen, combined with sandwiched radiotherapy, in newly diagnosed early-stage nasal natural killer/T-cell lymphoma (NKTCL...

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Main Authors: Huijuan Zhong, Shu Cheng, Jie Xiong, Jiayi Chen, Rongji Mu, Haoxu Yang, Hongmei Yi, Qi Song, Hao Zhang, Yu Hu, Guohui Cui, Juying Wei, Xi Zhang, Bing Xu, Wenbin Qian, Xiaobing Huang, Ming Hou, Feng Yan, Xin Wang, Yongping Song, Yuanhua Liu, Xuejun Ma, Jianda Hu, Fei Li, Chongyang Wu, Junmin Chen, Li Yu, Ou Bai, Jingyan Xu, Zunmin Zhu, Li Liu, Xin Zhou, Li Huang, Yin Tong, Ting Niu, Depei Wu, Xufeng Jiang, Chaofu Wang, Binshen Ouyang, Gang Cai, Biao Li, Jia Liu, Zhifeng Li, Rong Xiao, Luqun Wang, Yujie Jiang, Yanyan Liu, Xiaoyun Zheng, Pengpeng Xu, Li Wang, Saijuan Chen, Wei-Li Zhao
Format: Article
Language:English
Published: Ferrata Storti Foundation 2025-04-01
Series:Haematologica
Online Access:https://haematologica.org/article/view/12026
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Summary:The multi-center randomized phase 3 NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus 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. 256 eligible patients aged 14-70 years were randomly assigned (1:1) to ESA or MESA arm. The 5-year progression-free survival (PFS) rates were 80.3% and 74.9% in 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/progression 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 upregulated chromatin remodeling alterations, immune escape related genes, and decreased infiltrating monocytes/M1 macrophages. With low toxicity, non-intravenous and 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 clinical rationale in future mechanism-based therapy of NKTCL.
ISSN:0390-6078
1592-8721

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