Prognostic and predictive impact of neutrophil-to-lymphocyte ratio and HLA-I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy.

Background: Immune checkpoint inhibitors (ICIs) have become standard-of-care in patients with pretreated advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers for clinical outcomes are lacking for ICIs. The exploration of effective biomarkers is therefore needed to optimize patient benefit in the treatment of ESCC.

Methods: Sixty-nine patients with advanced ESCC enrolled at one center from two prospective trials were consecutively analyzed. NLR was dynamically collected and high-resolution HLA-I genotyping were performed on genomic DNA. Overall response rate (ORR), median progression-free survival (mPFS) and median overall survival (mOS) were investigated.

Results: Thirty-three (47.8%) of 69 patients with baseline NLR ≥4 demonstrated significantly worse clinical outcomes (ORR 9.1% vs. 36.1%, p = 0.018; mPFS 1.8 vs. 3.2 months, hazard ratio [HR] 1.79, p = 0.026; mOS 7.4 vs. 11.0 months, HR 2.28, p = 0.008). An NLR decrease ≥20% at the first radiological evaluation was associated with longer OS (median, 14.0 vs. 7.9 months, p = 0.038). Eleven (15.9%) patients with HLA-I homozygosity presented poorer clinical outcomes (ORR 0 vs. 27.6%, p = 0.056; mPFS 1.8 vs. 2.4 months, HR 3.37, p = 0.010; mOS 5.6 vs. 10.5 months, HR 3.97, p = 0.004). Patients with baseline NLR ≥4 and HLA-I homozygosity had the worst outcome (ORR 0; mPFS 1.4 months; mOS 1.8 months) among all. The association between NLR, HLA-I genotyping and clinical outcomes was independent of programmed death receptor ligand-1 expression.

Conclusions: NLR and HLA-I genotyping could have predictive and prognostic value in patients with advanced ESCC receiving camrelizumab, and the combination of biomarkers may help to identify more patient benefit from immunotherapy.