Inflammatory Blood Parameters as Biomarkers for Response to Immune Checkpoint Inhibition in Metastatic Melanoma Patients

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) have become a pillar of advanced melanoma treatment. Given the moderate response rate to ICIs in metastatic melanoma patients and the potentially severe toxicity of ICIs, the distinction between nonresponders and responders is crucial and challenging at the same time. Several biomarkers of response to immune checkpoint inhibition have been discussed in recent studies with conflicting results, and are so far not implemented in clinical routine. In this context, the validation of biomarkers obtained easily in clinical practice and predicting ICIs’ efficacy could improve the response rate and prevent nonresponders from immunotoxicity. Here, we provide evidence from a large cohort of metastatic melanoma patients that inflammatory blood parameters predicted the short- and long-term responses to ICIs with strong prediction power. Our results suggested the validation of inflammatory blood parameters as biomarkers predicting immunotherapies’ efficacity in metastatic melanoma patients. However, confounding factors interfering with myelopoiesis should also be taken into consideration. ABSTRACT: Objectives: We aimed to investigate whether inflammatory parameters in peripheral blood at baseline and during the first six months of treatment could predict the short- and long-term outcomes of metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs). Methods: This single-center retrospective study considered patients with metastatic melanoma treated with either single or dual checkpoint inhibition. Blood sample tests were scheduled together with (18)F-2-fluor-2-desoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans at baseline and at three and six months after initiation of ICI treatment. The short-term response to ICIs was assessed using FDG-PET/CT scans. The long-term response to ICIs was assessed using the overall survival OS and progression-free survival PFS as endpoints. Results: A total of 100 patients with metastatic melanoma were included (female, n = 31; male, n = 69). The median age was 68 years (interquartile range (IQR): 53–74 years). A total of 82% of the cohort displayed a disease control (DC), while 18% presented a progressive disease (PD) after six months of ICIs. Patients with DC after six months of ICIs showed a lower median of the neutrophils-to-lymphocytes ratio (NLR) toward patients with PD, with no significant prediction power of NLR neither in the short nor in the long term. The count of neutrophils at the baseline time point (TP 0) (p = 0.037) and erythrocytes three months after treatment start (TP 1) (p = 0.010) were strong predictive parameters of a DC six months after treatment start. Erythrocytes (p < 0.001) and lymphocytes (p = 0.021) were strong biomarkers predictive of a favorable OS. Erythrocytes (p = 0.013) and lymphocytes (p = 0.017) also showed a significant prediction power for a favorable PFS. Conclusions: Inflammatory blood parameters predicted the short- and long-term response to ICIs with a strong predictive power. Our results suggested the validation of inflammatory blood parameters as biomarkers that predict immunotherapies’ efficacity in metastatic melanoma patients. However, confounding factors that interfere with myelopoiesis should also be taken into consideration.