Haematologica (Apr 2025)
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
- 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
Affiliations
- Huijuan Zhong
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Shu Cheng
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Jie Xiong
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Jiayi Chen
- Department of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Rongji Mu
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai
- Haoxu Yang
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Hongmei Yi
- Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Qi Song
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Hao Zhang
- Department of Otolaryngology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Yu Hu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
- Guohui Cui
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
- Juying Wei
- Department of Hematology, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang
- Xi Zhang
- Department of Hematology, Xinqiao Hospital, Chongqing
- Bing Xu
- Department of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian
- Wenbin Qian
- Department of Hematology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang
- Xiaobing Huang
- Institute of Hematology, Department of Hematology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan
- Ming Hou
- Department of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong
- Feng Yan
- Department of Hematology, Third Affiliated Hospital of Suzhou University, First People’s Hospital of Changzhou, Changzhou, Jiangsu
- Xin Wang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong
- Yongping Song
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan
- Yuanhua Liu
- Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu
- Xuejun Ma
- Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai
- Jianda Hu
- Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian
- Fei Li
- Department of Hematology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi
- Chongyang Wu
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou, Gansu
- Junmin Chen
- Department of Hematology and Rheumatology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian
- Li Yu
- Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi
- Ou Bai
- Department of Hematology, First Hospital of Jilin University, Changchun, Jilin
- Jingyan Xu
- Department of Hematology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu
- Zunmin Zhu
- Department of Hematology, Henan Province People’s Hospital, Zhengzhou, Henan
- Li Liu
- Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shanxi
- Xin Zhou
- Department of Hematology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu
- Li Huang
- Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan
- Yin Tong
- Department of Hematology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, Shanghai
- Ting Niu
- Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan
- Depei Wu
- First Affiliated Hospital of Soochow University, Suzhou, Jiangsu
- Xufeng Jiang
- Department of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Chaofu Wang
- Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Binshen Ouyang
- Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Gang Cai
- Department of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Biao Li
- Department of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Jia Liu
- Department of Hematology, Xinqiao Hospital, Chongqing
- Zhifeng Li
- Department of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian
- Rong Xiao
- Institute of Hematology, Department of Hematology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan
- Luqun Wang
- Department of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong
- Yujie Jiang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong
- Yanyan Liu
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan
- Xiaoyun Zheng
- Department of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian
- Pengpeng Xu
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Li Wang
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
- Saijuan Chen
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai
- Wei-Li Zhao
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai
- DOI
- https://doi.org/10.3324/haematol.2025.287513
- Journal volume & issue
-
Vol. 999,
no. 1
Abstract
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.
