Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma

Abstract

Background

To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM).

Methods

We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve.

Results

At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months).

Conclusions

Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.