The Innovation (May 2023)
Etoposide, dexamethasone, and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma: A randomized phase III study
- Huijuan Zhong,
- Shu Cheng,
- Xi Zhang,
- Bing Xu,
- Jiayi Chen,
- Xufeng Jiang,
- Jie Xiong,
- Yu Hu,
- Guohui Cui,
- Juying Wei,
- Wenbin Qian,
- Xiaobing Huang,
- Ming Hou,
- Feng Yan,
- Xin Wang,
- Yongping Song,
- Jianda Hu,
- Yuanhua Liu,
- Xuejun Ma,
- 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,
- Hao Zhang,
- Chaofu Wang,
- Binshen Ouyang,
- Hongmei Yi,
- Qi Song,
- Gang Cai,
- Biao Li,
- Jia Liu,
- Zhifeng Li,
- Rong Xiao,
- Luqun Wang,
- Yujie Jiang,
- Yanyan Liu,
- Xiaoyun Zheng,
- Pengpeng Xu,
- Hengye Huang,
- Li Wang,
- Saijuan Chen,
- Weili 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 200025, China
- 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 200025, China
- Xi Zhang
- Department of Hematology, Xinqiao Hospital, Chongqing 400037, China
- Bing Xu
- Department of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361009, China
- Jiayi Chen
- Department of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Xufeng Jiang
- Department of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- 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 200025, China
- Yu Hu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
- Guohui Cui
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
- Juying Wei
- Department of Hematology, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
- Wenbin Qian
- Department of Hematology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China
- Xiaobing Huang
- Institute of Hematology, Department of Hematology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, China
- Ming Hou
- Department of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China
- Feng Yan
- Department of Hematology, Third Affiliated Hospital of Suzhou University, First People’s Hospital of Changzhou, Changzhou, Jiangsu 213004, China
- Xin Wang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China
- Yongping Song
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450003, China
- Jianda Hu
- Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350401, China
- Yuanhua Liu
- Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, China
- Xuejun Ma
- Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
- Fei Li
- Department of Hematology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- Chongyang Wu
- Department of Hematology, Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China
- Junmin Chen
- Department of Hematology and Rheumatology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, China
- Li Yu
- Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China
- Ou Bai
- Department of Hematology, First Hospital of Jilin University, Changchun, Jilin 130061, China
- Jingyan Xu
- Department of Hematology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, China
- Zunmin Zhu
- Department of Hematology, Henan Province People’s Hospital, Zhengzhou, Henan 450003, China
- Li Liu
- Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shanxi 710032, China
- Xin Zhou
- Department of Hematology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, China
- Li Huang
- Department of Oncology and Hematology, Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan 646000, China
- Yin Tong
- Department of Hematology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200080, China
- Ting Niu
- Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Depei Wu
- First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China
- Hao Zhang
- Department of Otolaryngology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Chaofu Wang
- Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Binshen Ouyang
- Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Hongmei Yi
- Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Qi Song
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Gang Cai
- Department of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Biao Li
- Department of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Jia Liu
- Department of Hematology, Xinqiao Hospital, Chongqing 400037, China
- Zhifeng Li
- Department of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361009, China
- Rong Xiao
- Institute of Hematology, Department of Hematology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, China
- Luqun Wang
- Department of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China
- Yujie Jiang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China
- Yanyan Liu
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450003, China
- Xiaoyun Zheng
- Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350401, China
- 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 200025, China
- Hengye Huang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- 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 200025, China
- 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 200025, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai 200025, China
- Weili 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 200025, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai 200025, China; Corresponding author
- Journal volume & issue
-
Vol. 4,
no. 3
p. 100426
Abstract
Methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). We explored the efficacy and safety of reduced-intensity, non-intravenous etoposide, dexamethasone, and pegaspargase (ESA) with sandwiched radiotherapy. This multicenter, randomized, phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China. Patients were randomly assigned (1:1) to receive ESA (pegaspargase 2,500 IU/m2 intramuscularly on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2–4) or MESA (methotrexate 1 g/m2 intravenously on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2–4, and pegaspargase 2,500 IU/m2 intramuscularly on day 5) regimen (four cycles), combined with sandwiched radiotherapy. The primary endpoint was overall response rate (ORR). The non-inferiority margin was −10.0%. From March 16, 2016, to July 17, 2020, 256 patients underwent randomization, and 248 (ESA [n = 125] or MESA [n = 123]) made up the modified intention-to-treat population. The ORR was 88.8% (95% confidence interval [CI], 81.9–93.7) for ESA with sandwiched radiotherapy and 86.2% (95% CI, 78.8–91.7) for MESA with sandwiched radiotherapy, with an absolute rate difference of 2.6% (95% CI, −5.6–10.9), meeting the non-inferiority criteria. Per-protocol and sensitivity analysis supported this result. Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.
