早期血浆 Epstein-Barr 病毒 DNA 载量和病毒裂解基因组水平的变化可预测程序性细胞死亡受体 1 单药治疗复发性或转移性鼻咽癌的临床结局。
Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy.
机构信息
Department of Clinical Research, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, P. R. China.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, P. R. China.
出版信息
BMC Cancer. 2024 Jul 3;24(1):797. doi: 10.1186/s12885-024-12564-4.
PURPOSE
Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials.
METHODS
Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples.
RESULTS
We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS.
CONCLUSION
In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.
目的
复发或转移性鼻咽癌（RM-NPC）患者从抗程序性死亡 1（anti-PD-1）单药治疗中获益已得到证实。在这里，我们回顾性分析了来自 2 项注册的 I 期试验的血浆 EBV 病毒（EBV）DNA 载量和肿瘤病毒裂解基因组与临床结局之间的关联。
方法
纳入 2016 年 3 月至 2018 年 1 月期间来自 Checkmate 077（在中国进行的 nivolumab I 期试验）和卡瑞利珠单抗 I 期试验的 RM-NPC 患者。对 68 例患者进行了基线 EBV DNA 滴度检测，对至少有 3 个基线后 EBV 数据时间点和至少 1 个基线后放射学评估时间点的 60 例患者进行了 EBV 评估。我们将“EBV 反应”定义为连续 3 次负荷低于基线的 50%，“EBV 进展”定义为连续 3 次负荷高于基线的 150%。对 60 例有可用肿瘤样本的患者进行了全外显子组测序。
结果
我们发现，基线 EBV DNA 载量与肿瘤大小呈正相关（斯皮尔曼 p<0.001）。部分缓解（PR）和疾病稳定（SD）患者的 EBV 载量明显低于进展疾病（PD）患者。EBV 评估与放射学评估高度一致。与 EBV 进展的患者相比，EBV 反应的患者的总生存期（OS）显著提高（对数秩检验 p=0.004，HR=0.351[95%CI：0.171-0.720]，中位 22.5 个月 vs. 11.9 个月）。与初始放射学反应和进展相比，初始 EBV 反应和进展的中位时间分别为 25 天和 36 天。基线时 EBV 裂解基因水平较高的患者，包括 BKRF2、BKRF3 和 BKRF4，其无进展生存期（PFS）和 OS 更好。
结论
总之，在接受抗 PD-1 单药治疗的 RM-NPC 患者中，血浆 EBV DNA 载量的早期清除和高水平的裂解 EBV 基因与更好的临床结局相关。
Zotero 插件