CARAMEL study: Clinical prognostic biomarkers for ipilimumab-related outcome in metastatic melanoma patients

Abstract

Background: Ipilimumab is an inhibitor of CTLA4 receptor of T lymphocytes approved by the FDA both as first and second line treatment for patients with metastatic melanoma. Despite the efficacy observed in about 20% of patients, it still remains a therapy with a considerable outlay, both from an economic and safety point of view: the aim of our study was to explore prognostic biomarkers among hematological parameters normally used in clinical practice. Methods: This is a retrospective multicenter study which enrolled 120 patients with hystologically confirmed metastatic melanoma treated with Ipilimumab between January 2013 and January 2016 (mean age 62.2 ± 14.58). Full blood count with absolute WBC (aWBC), neutrophil count, eosinophil count, neutrophil/lymphocyte ratio (NLR), platelets/lymphocyte ratio (PLR) and LDH serum levels were assessed at baseline and every 3 weeks during treatment. We evaluated the mutational BRAF status and the number of metastatic sites involved before treatment (more or less than 3 sites). The cut‐off values for our parameters were determined with time‐dependent receiver operating characteristic (ROC) analysis. To identify prognostic and predictive biomarkers the above parameters have been correlated with Progression‐Free Survival (PFS) and Overall Survival (OS). Results: After a median follow up of 21 months, median PFS was 4 months and median OS was 17 months. Patients with low serum LDH levels at baseline had significantly longer PFS (p = 0.018) and OS (p < 0.05). Higher NLR (p = 0.043) and PLR values (p < 0.05) were related to worse PFS. Interestingly, we found that women had shorter OS (p = 0.002) and PFS (p = 0.003) compared with men. The presence of >3 sites of metastases seems to be correlated to a worse OS (p < 0.04) and PFS (p < 0.03). Conclusions: Although these findings need to be confirmed and validated and the multivariate analysis is still in progress, we suggest that the parameters explored in our study, which are normally assessed in clinical practice, may be useful to assist disease‐management strategies for advanced melanoma patients.