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.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеКлиническое исследование III фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhong Huijuan, Cheng Shu, Xiong Jie, Chen Jiayi, Mu Rongji, Yang Haoxu, Yi Hongmei, Song Qi, Zhang Hao, Hu Yu, Cui Guohui, Wei Juying, Zhang Xi, Xu Bing, Qian Wenbin, Huang Xiaobing, Hou Ming, Yan Feng, Wang Xin, Song Yongping, Liu Yuanhua, Ma Xuejun, Hu Jianda, Li Fei, Wu Chongyang, Chen Junmin, Yu Li, Bai Ou, Xu Jingyan, Zhu Zunmin, Liu Li, Zhou Xin, Huang Li, Tong Yin, Niu Ting, Wu Depei, Jiang Xufeng, Wang Chaofu, Ouyang Binshen, Cai Gang, Li Biao, Liu Jia, Li Zhifeng, Xiao Rong, Wang Luqun, Jiang Yujie, Liu Yanyan, Zheng Xiaoyun, Xu Pengpeng, Wang Li, Chen Saijuan, Zhao Wei-Li
Аннотация
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.