Ge Song,1,* Zhigong Wei,2,* Yiyan Pei,1 Zheran Liu,1 Yu Min,1 Huilin Li,1 Kun Gao,1 Junyou Ge,3 Yan Qing,3 Youneng Wei,3 Ye Chen,2,4 Xingchen Peng1 

1Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, People’s Republic of China; 4Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xingchen Peng, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-13458502834, Fax +86-28-85423278, Email pxx2014@scu.edu Ye Chen, Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980605508, Fax +86-028-85422589, Email huaxichenye@163.com

Purpose: Immunotherapy has become the primary option for recurrent and metastatic nasopharyngeal cancer (R/M NPC) after failure of chemotherapy, but without good prognostic indicators. Our study aimed to assess the potential of the systemic immune-inflammation index (SII) in predicting the effectiveness of PD-L1 inhibitor therapy for R/M NPC.
Patients and Methods: The study cohort comprises of a prospective Phase 2 clinical trial population undergoing PD-L1 inhibitor for R/M NPC at 42 hospitals in China between 2019 and 2021. The SII is classified into high and low states based on the optimal threshold determined by the ROC curve. We assessed the relationship between SII status and objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) using regression analyses and Kaplan–Meier method. We performed sensitivity analyses to confirm the results.
Results: Our study analyzed 153 patients from one of the largest cohorts to date of R/M NPC treated with PD-L1 inhibitor and found that SII showed a significant association with prognosis. We found higher ORR and DCR in the SII-Low group. Univariate analyses demonstrated that SII independently predicted DCR (OR, 0.43; 95% CI, 0.22– 0.84; p = 0.001), PFS (HR, 1.85; 95% CI, 1.31– 2.62; p < 0.001) and OS (HR, 1.92; 95% CI, 1.29– 2.85; p < 0.001). After adjusting for covariates, multivariate analysis remains relevant. [DCR (OR, 0.47; 95% CI, 0.22– 0.99; p = 0.048), PFS (HR, 1.72; 95% CI, 1.2– 2.47; p =0.003); OS (HR, 2.08; 95% CI, 1.38– 3.13; p < 0.001)]. Sensitivity analyses also support this conclusion.
Conclusion: SII may well provide predictive value for the efficacy and prognosis of patients with R/M NPC treated with PD-L1 inhibitor. Patients with high status of SII may have a poorer therapeutic effect and survival.

Keywords: systemic immune response, nasopharyngeal carcinoma prognosis, immunotherapy, efficacy