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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Ferrata Storti Foundation
2025-04-01
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| Series: | Haematologica |
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| author | 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 |
| author_facet | 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 |
| author_sort | Huijuan Zhong |
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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.
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| language | English |
| publishDate | 2025-04-01 |
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| series | Haematologica |
| spelling | doaj-art-2bce5d0a11934151b370c0900518bcc92025-08-20T02:16:28ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-04-01999110.3324/haematol.2025.287513Dynamic 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 studyHuijuan Zhong0Shu Cheng1Jie Xiong2Jiayi Chen3Rongji Mu4Haoxu Yang5Hongmei Yi6Qi Song7Hao Zhang8Yu Hu9Guohui Cui10Juying Wei11Xi Zhang12Bing Xu13Wenbin Qian14Xiaobing Huang15Ming Hou16Feng Yan17Xin Wang18Yongping Song19Yuanhua Liu20Xuejun Ma21Jianda Hu22Fei Li23Chongyang Wu24Junmin Chen25Li Yu26Ou Bai27Jingyan Xu28Zunmin Zhu29Li Liu30Xin Zhou31Li Huang32Yin Tong33Ting Niu34Depei Wu35Xufeng Jiang36Chaofu Wang37Binshen Ouyang38Gang Cai39Biao Li40Jia Liu41Zhifeng Li42Rong Xiao43Luqun Wang44Yujie Jiang45Yanyan Liu46Xiaoyun Zheng47Pengpeng Xu48Li Wang49Saijuan Chen50Wei-Li Zhao51Shanghai 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, ShanghaiShanghai 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, ShanghaiShanghai 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, ShanghaiDepartment of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiClinical Research Institute, Shanghai Jiao Tong University School of Medicine, ShanghaiShanghai 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, ShanghaiDepartment of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Otolaryngology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HubeiInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HubeiDepartment of Hematology, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ZhejiangDepartment of Hematology, Xinqiao Hospital, ChongqingDepartment of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, FujianDepartment of Hematology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ZhejiangInstitute of Hematology, Department of Hematology, Sichuan Provincial People’s Hospital, Chengdu, SichuanDepartment of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, ShandongDepartment of Hematology, Third Affiliated Hospital of Suzhou University, First People’s Hospital of Changzhou, Changzhou, JiangsuDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShandongDepartment of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, HenanDepartment of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, JiangsuDepartment of Medical Oncology, Shanghai Cancer Center, Fudan University, ShanghaiDepartment of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, FujianDepartment of Hematology, First Affiliated Hospital of Nanchang University, Nanchang, JiangxiDepartment of Hematology, Second Hospital of Lanzhou University, Lanzhou, GansuDepartment of Hematology and Rheumatology, First Affiliated Hospital of Fujian Medical University, Fuzhou, FujianDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, JiangxiDepartment of Hematology, First Hospital of Jilin University, Changchun, JilinDepartment of Hematology, Nanjing Drum Tower Hospital, Nanjing, JiangsuDepartment of Hematology, Henan Province People’s Hospital, Zhengzhou, HenanDepartment of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, ShanxiDepartment of Hematology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, JiangsuDepartment of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, SichuanDepartment of Hematology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, ShanghaiDepartment of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, SichuanFirst Affiliated Hospital of Soochow University, Suzhou, JiangsuDepartment of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ShanghaiDepartment of Hematology, Xinqiao Hospital, ChongqingDepartment of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, FujianInstitute of Hematology, Department of Hematology, Sichuan Provincial People’s Hospital, Chengdu, SichuanDepartment of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, ShandongDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShandongDepartment of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, HenanDepartment of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, FujianShanghai 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, ShanghaiShanghai 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, ShanghaiShanghai 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, ShanghaiShanghai 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 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. https://haematologica.org/article/view/12026 |
| spellingShingle | 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 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 Haematologica |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://haematologica.org/article/view/12026 |
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