Chemotherapy combined with immune checkpoint inhibitors may overcome the detrimental effect of high neutrophil-to-lymphocyte ratio prior to treatment in esophageal cancer patients

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option for esophageal cancer (EC). Although ICIs enable long-term survival in some patients, the efficacy of ICIs varies widely among patients. Therefore, predictive biomarkers are necessary for identifying patients who are most likely to benefit from ICIs to improve the efficacy of the treatment. We retrospectively analyzed the outcomes of combination therapy, including nivolumab plus ipilimumab or chemotherapy plus anti-programmed cell death 1 (PD-1) antibodies in our institute to identify biomarkers.

Methods: Twenty-seven patients received nivolumab plus ipilimumab, and thirty-six patients received chemotherapy plus anti-PD-1 antibodies were included in this study. We analyzed patient characteristics, efficacy, and safety. Multivariable analysis of biomarkers evaluated the correlation among overall survival (OS), progression-free survival (PFS), and the following variables: body mass index, performance status, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein level, and albumin level before treatment.

Results: In multivariable analysis, albumin level was significantly correlated with PFS in the cisplatin plus 5-fluorouracil (CF) plus pembrolizumab group. NLR and albumin level were significantly correlated with OS in the nivolumab plus ipilimumab group. Other variables, including PS, BMI, and CRP did not correlate with any of the outcomes.

Conclusions: High NLR in EC patients prior to treatment was significantly less effective for ICIs. In chemotherapy combined with ICIs, NLR before the treatment was not associated with treatment efficacy, suggesting combination chemotherapy may be beneficial for EC patients with high NLR. NLR may be an indicator of immunocompetence in anti-tumor immunity and a convenient predictive biomarker for selecting appropriate treatments including ICIs.