Min Fang,1,2,* Yujun Hu,3,4,* Tiejun Wang,5,* Yong Su,2,6 Tianzhu Lu,2,6 Hao Zhang,7 Jingao Li,2,6 Chuanmiao Xie,3,4,* Xiaochang Gong2,6,* 

1Department of Oncology, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, 330000, People’s Republic of China; 2NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, 330029, People’s Republic of China; 3Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 5Breast cancer center, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 6Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, 330029, People’s Republic of China; 7Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiaochang Gong, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Nanchang, People’s Republic of China, Email gxcanddw@163.com Chuanmiao Xie, Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China, Email xiechm@sysucc.org.cn

Purpose: This study investigates the predictive value of early C-reactive protein (CRP) kinetics in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving first-line chemotherapy combined with anti-PD-1 mAbs (first-line chemoimmunotherapy).
Patients and Methods: Patients were categorized into three groups based on early CRP kinetics within one and three months after the start of immunotherapy: (1) CRP flare-responders, with CRP levels rising to more than double the baseline within one month and subsequently falling below baseline within three months; (2) CRP non-flare-responders, with CRP levels decreasing by more than 30% within three months without initial flare; (3) CRP non-responders, with no significant CRP changes. Associations with objective response rate (ORR), and progression-free survival (PFS) were evaluated.
Results: The multicenter study included 149 patients with dmNPC (median follow-up: 22 months). The cohort comprised 39 (26.2%) CRP flare-responders, 76 (51%) CRP non-flare-responders, and 34 (22.8%) CRP non-responders. CRP flare-responders and non-flare-responders were combined into CRP responders, showing significantly improved ORR (94.8% vs 79.4%, P=0.009) and prolonged median PFS (20 vs 13 months, P=0.006) compared to CRP non-responders. Multivariable analysis identified early CRP kinetics as an independent prognostic factor for PFS (HR=2.688, 95% CI: 1.484– 4.868, P< 0.001). In subgroup analysis, patients with undetectable EBV DNA after three immunotherapy cycles showed higher median PFS among CRP responders compared to non-responders (28 vs 21 months, P=0.014), whereas no significant difference was observed in patients with detectable EBV DNA levels (13 vs 8 months, P=0.142).
Conclusion: CRP responders are associated with improved survival outcomes, particularly in patients achieving early EBV DNA clearance. Early CRP kinetics combined with early plasma EBV DNA clearance may be predictive of survival outcomes in dmNPC patients receiving first-line chemoimmunotherapy.

Keywords: de novo metastatic nasopharyngeal carcinoma, biomarker, immunotherapy, C-reactive protein, Epstein Barr virus DNA