Background: Ipilimumab is an inhibitor of CTLA4 receptor of T lymphocytes that has been approved by FDA both as first and second line treatment for patients with metastatic melanoma. Despite the efficacy reported in literature is very promising, it still remain a therapy with a considerable outlay, both from an economic and safety point of view. Therefore, it is relevant to identify in advance which patients could benefit from treatment: the aim of our study is validate predictive biomarkers of treatment efficacy 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. To date 70 patients are completely evaluable (mean age 62.2±14.58). They received Ipilimumab as first line (35 patients, 50%), as second line (31 patients, 44.3%) or as third line treatment (4 patients, 5.7%). We assessed before and regularly every 3 weeks the full blood count with absolute WBC (aWBC), neutrophil count, neutrophil/lymphocyte ratio (NLR) and LDH serum levels. We evaluated the mutational BRAF status and the number of metastatic sites involved before and after treatment. The cut-off value for aWBC and LDH 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 the median PFS was 6 months and the median OS was 9 months. We found a significant inverse correlation between PFS and LDH (p = 0.018) and aWBC values (p = 0.0062). As for survival analysis high LDH (HR 8.390; 95% CI 5.865 - 118.3; p < 0.001) and high NLR (HR 2.972; 95% CI 1.035 - 8.530; p = 0.043) were related to worse PFS. Conclusions: The OS analysis in still in progress, but these data are very promising and, if confirmed, they really could help us to better manage the correct therapeutic sequence for treatment of metastatic melanoma patients.

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

Natoli, Clara;
2016

Abstract

Background: Ipilimumab is an inhibitor of CTLA4 receptor of T lymphocytes that has been approved by FDA both as first and second line treatment for patients with metastatic melanoma. Despite the efficacy reported in literature is very promising, it still remain a therapy with a considerable outlay, both from an economic and safety point of view. Therefore, it is relevant to identify in advance which patients could benefit from treatment: the aim of our study is validate predictive biomarkers of treatment efficacy 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. To date 70 patients are completely evaluable (mean age 62.2±14.58). They received Ipilimumab as first line (35 patients, 50%), as second line (31 patients, 44.3%) or as third line treatment (4 patients, 5.7%). We assessed before and regularly every 3 weeks the full blood count with absolute WBC (aWBC), neutrophil count, neutrophil/lymphocyte ratio (NLR) and LDH serum levels. We evaluated the mutational BRAF status and the number of metastatic sites involved before and after treatment. The cut-off value for aWBC and LDH 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 the median PFS was 6 months and the median OS was 9 months. We found a significant inverse correlation between PFS and LDH (p = 0.018) and aWBC values (p = 0.0062). As for survival analysis high LDH (HR 8.390; 95% CI 5.865 - 118.3; p < 0.001) and high NLR (HR 2.972; 95% CI 1.035 - 8.530; p = 0.043) were related to worse PFS. Conclusions: The OS analysis in still in progress, but these data are very promising and, if confirmed, they really could help us to better manage the correct therapeutic sequence for treatment of metastatic melanoma patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/699595
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