[Serum interleukin predicts the efficacy of immunotherapy for nasopharyngeal carcinoma: a prospective observational study].

Objectives: To explore the correlation between the changes in serum interleukin-8 (IL-8) and interleukin-6 (IL-6) levels and the efficacy of anti-programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors in patients with recurrent and metastatic nasopharyngeal carcinoma. Trying to identify predictive indicators for the efficacy of anti-PD-1/PD-L1 inhibitors in these patients. Methods: A prospective analysis was conducted on the clinical and laboratory data of 80 patients diagnosed with recurrent and metastatic nasopharyngeal carcinoma at Huadong Hospital from January 2022 to December 2024. Fasting peripheral blood (3 ml) was collected from patients at baseline, 2-4 weeks after the start of treatment, and at each follow-up visit to measure IL-8 and IL-6 levels, and the correlation between these levels and the efficacy of anti-PD-1/PD-L1 inhibitors was analyzed. Results: The median age of the patients was 62 years old, and 80 cases completed the follow-up. According to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), patients with best responses of complete response, partial response, and stable disease were defined as responders; those with best responses of progressive disease were defined as non-responders. In responders, the median serum IL-8 level at best response (BR) was significantly lower than that at baseline (BL) [BL: 34.6(26.9, 65.2) pg/ml, BR: 11.6(9.4, 32.6) pg/ml; P＜0.001], and significantly increased at progressive disease (PD)[BR: 11.6(9.4, 32.6) pg/ml, PD: 79.0(44.55, 107.7) pg/ml, P＜0.001]. In non-responders, the median serum IL-8 level at PD was significantly higher than that at BL[BL: 30.5(24.6, 77.5) pg/ml, PD: 80.95(68.45, 117.25) pg/ml; P＜0.001]. The early changes in serum IL-8 levels (2-4 weeks after the first dose) were associated with the efficacy of anti-PD-1/PD-L1 inhibitors [responders: -38.6%(-47.2%, -11.8%); non-responders: 44.5%(3.5%, 59.8%), P＜0.001]. With a cut-off value of -8.85% for the percentage change in serum IL-8 levels from BL to 2-4 weeks, the area under the curve (AUC) was 0.913 (95% CI: 0.853-0.973; P＜0.001), the specificity was 80.9% (95% CI: 66.7%-90.9%), and the sensitivity was 87.9% (95% CI: 71.8%-96.6%). Patients were divided into two groups based on the early change ratio of IL-8:＜-8.85% change group and ≥-8.85% change group. There were 4 deaths in the <-8.85% change group and 10 deaths in the ≥-8.85% change group. The 24-month cumulative survival rate in the -8.85% change group was significantly higher than that in the ≥-8.85% change group (85.1% vs. 70.2%, P=0.025). The risk of death in the ≥-8.85% change group was 3.392 times higher than that of the < -8.85% change group(HR=3.392 ,95% CI: 1.175-9.789). In responders, the serum IL-6 level at PD was significantly higher than that at BR[BR: 4.3(2.6,8.8) pg/ml, PD: 11.4(4.7,25.3) pg/ml, P＜0.001]. In non-responders, the serum IL-6 level at PD was significantly higher than that at BL [BL: 7.9(4.5,17.2) pg/ml, PD: 15.9(7.3,23.3) pg/ml, P=0.030]. The early changes in serum IL-6 levels were not associated with the efficacy of anti-PD-1/PD-L1 inhibitors[responders: -0.12%(-0.39%, 0.27%); non-responders: 0.05%(-0.13%, 0.20%), P=0.059]. Conclusions: The changes in serum IL-8 and IL-6 levels are associated with the efficacy of anti-PD-1/PD-L1 inhibitors in patients, which may be effective and easily assessable biomarkers for predicting the efficacy of anti-PD-1/PD-L1 inhibitors in patients with recurrent and metastatic nasopharyngeal carcinoma. An early decline in serum IL-8 levels (2-4 weeks after the first administration) is positively correlated with the efficacy of anti-PD-1/PD-L1 inhibitors.