Trajectories of Plasma Epstein–Barr Virus DNA and Clinical Outcomes in Recurrent or Metastatic Nasopharyngeal Carcinoma Treated With PD ‐ L1 Inhibitors: A Post‐Hoc Analysis of a Multicenter, Phase II Study

ABSTRACT Background Reliable biomarkers for predicting clinical outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) treated with immunotherapy remain limited. This study evaluated the association between longitudinal EBV DNA trajectories and clinical outcomes in patients with R/M NPC receiving immune checkpoint inhibitors. Methods This post hoc analysis used data from a multicenter, single‐arm, Phase II trial evaluating the programmed cell death‐ligand 1 (PD‐L1) inhibitor KL‐A167 in patients with previously treated R/M NPC. Plasma EBV DNA was measured at baseline and at each scheduled efficacy assessment, which was conducted every six weeks until disease progression. EBV DNA trajectories were distinguished through a logistic trajectory model. Multivariable Cox models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for survival outcomes. Results We identified three distinct trajectories: persistently undetectable ( n  = 17, 13.8%), fluctuating ( n  = 40, 32.5%), and persistently detectable ( n  = 66, 53.7%). Compared with the persistently undetectable group, HRs of death were 4.96 (95% CI, 1.60–15.40) and 12.59 (95% CI, 4.01–39.51) for the fluctuating and persistently detectable groups, respectively. HRs of disease progression were 1.96 (95% CI, 0.97–3.96) and 3.22 (95% CI, 1.56–6.67), respectively. Conclusion This study suggests that plasma EBV DNA trajectories could be a promising biomarker for monitoring treatment response and longitudinal risk stratification.