Integrating neutrophils, lymphocytes and eosinophils: development and validation of the NLE Index in ICI-treated metastatic melanoma

Prognosis for metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs) remains heterogeneous. Although neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) are established markers, we hypothesized a neutrophil-to-lymphocyte-times-eosinophil (NLE) index would offer superior stratification. We analyzed 194 metastatic melanoma patients receiving ICIs, divided into training ( n = 129) and validation ( n = 65) cohorts. An optimal NLE cutoff categorized patients as NLE-low or NLE-high. Survival outcomes and objective response rate (ORR) were assessed using Kaplan-Meier, Cox regression, and logistic regression. Predictive accuracy of NLE, NLR, and NER was compared. Median overall survival was significantly longer in NLE-low versus NLE-high patients (training: 31.3 versus 6.9 months; P = 0.011; validation: 33.5 versus 9.1 months; P = 0.019). Median progression-free survival also improved significantly in NLE-low patients (training: 10.6 versus 3.1 months; P = 0.029; validation: 13.7 versus 3.9 months; P = 0.012). ORR was higher in NLE-low groups (training: 46.0% versus 13.2%; P < 0.001; validation: 43.6% versus 18.2%; P = 0.078). NLE demonstrated superior predictive accuracy compared with NLR and NER. The NLE index outperforms NLR and NER in predicting survival and response in metastatic melanoma patients treated with ICIs, providing a practical clinical tool.