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.

Neutrophil‐to‐eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti‐PD‐1 therapy

“…2.46, 95% CI: 1.77-3.43) and PFS (HR: 2.38, 95% CI: 1.95-2.89). In a recent report, (Guida et al, 2022). identified an association between ing IL-8 and both peripheral neutrophil counts and tumor infiltrating neutrophilis as well as a negative association with response rates and survival outcomes (Schalper et al, 2020).…”

Baseline neutrophil-to- ratio combined with the change during treatment provides risk stratification for metastatic malignant melanoma patients treated with PD-1 inhibitors in a Chinese population

“…At present, the cut-off values of BLNLR and DNLR% in predicting the prognosis of patients with advanced melanoma have not been unified. BLNLR is often used as the cut-off value of 3, 4, or 5 (18,19,25) and DNLR% is often used as the cut-off value of 30% (21,23). In this study, 3 and 30% were selected as the cut-off values for BLNLR and DNLR% respectively.…”

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab

“…Furthermore, tumor-associated thrombocytosis has been linked to poor clinical outcomes in several cancers, including pancreatic cancer, hepatocellular carcinoma, renal cell carcinoma or glioblastoma ( 15 , 35 – 38 ), and it recently has been significantly associated with a poorer prognosis in lung cancer and melanoma patients receiving immunotherapy ( 39 – 41 ). Rachidi et al.…”