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A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab

SIMPLE SUMMARY: Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, improves the survival of patients with advanced melanoma. This study aimed to investigate the association of baseline clinical characteristics, laboratory and imaging variables, and gene expression profiling scor...

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Autores principales: Awada, Gil, Jansen, Yanina, Schwarze, Julia Katharina, Tijtgat, Jens, Hellinckx, Lennert, Gondry, Odrade, Vermeulen, Sim, Warren, Sarah, Schats, Kelly, van Dam, Pieter-Jan, Kockx, Mark, Keyaerts, Marleen, Everaert, Hendrik, Seremet, Teofila, Rogiers, Anne, Neyns, Bart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825041/
https://www.ncbi.nlm.nih.gov/pubmed/33418936
http://dx.doi.org/10.3390/cancers13020168
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author Awada, Gil
Jansen, Yanina
Schwarze, Julia Katharina
Tijtgat, Jens
Hellinckx, Lennert
Gondry, Odrade
Vermeulen, Sim
Warren, Sarah
Schats, Kelly
van Dam, Pieter-Jan
Kockx, Mark
Keyaerts, Marleen
Everaert, Hendrik
Seremet, Teofila
Rogiers, Anne
Neyns, Bart
author_facet Awada, Gil
Jansen, Yanina
Schwarze, Julia Katharina
Tijtgat, Jens
Hellinckx, Lennert
Gondry, Odrade
Vermeulen, Sim
Warren, Sarah
Schats, Kelly
van Dam, Pieter-Jan
Kockx, Mark
Keyaerts, Marleen
Everaert, Hendrik
Seremet, Teofila
Rogiers, Anne
Neyns, Bart
author_sort Awada, Gil
collection PubMed
description SIMPLE SUMMARY: Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, improves the survival of patients with advanced melanoma. This study aimed to investigate the association of baseline clinical characteristics, laboratory and imaging variables, and gene expression profiling scores on tumor tissue analysis of advanced melanoma patients who were treated with pembrolizumab, with survival using univariate and multivariate analysis. Baseline organ function (reflected by the presence of active brain metastases, number of metastatically affected organs, albumin) and systemic inflammatory/immunologic status (reflected by albumin, C-reactive protein, absolute lymphocyte count, neutrophil-to-lymphocyte ratio) are the most important clinical and/or laboratory parameters predictive of survival. Novel biomarkers include the baseline presence of BRAF(V600) or NRAS(Q61/G12/G13) mutant circulating tumor DNA and baseline total metabolic tumor volume assessed by whole-body (18)F-FDG-PET/CT. Gene expression profiling scores by the NanoString PanCancer IO360 panel were not conclusive in our patient population. ABSTRACT: Background: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted. Methods: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival. Results: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline (18)F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm(3) delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm(3). No significant associations were observed between baseline GEP scores and survival. Conclusion: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab.
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spelling pubmed-78250412021-01-24 A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab Awada, Gil Jansen, Yanina Schwarze, Julia Katharina Tijtgat, Jens Hellinckx, Lennert Gondry, Odrade Vermeulen, Sim Warren, Sarah Schats, Kelly van Dam, Pieter-Jan Kockx, Mark Keyaerts, Marleen Everaert, Hendrik Seremet, Teofila Rogiers, Anne Neyns, Bart Cancers (Basel) Article SIMPLE SUMMARY: Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, improves the survival of patients with advanced melanoma. This study aimed to investigate the association of baseline clinical characteristics, laboratory and imaging variables, and gene expression profiling scores on tumor tissue analysis of advanced melanoma patients who were treated with pembrolizumab, with survival using univariate and multivariate analysis. Baseline organ function (reflected by the presence of active brain metastases, number of metastatically affected organs, albumin) and systemic inflammatory/immunologic status (reflected by albumin, C-reactive protein, absolute lymphocyte count, neutrophil-to-lymphocyte ratio) are the most important clinical and/or laboratory parameters predictive of survival. Novel biomarkers include the baseline presence of BRAF(V600) or NRAS(Q61/G12/G13) mutant circulating tumor DNA and baseline total metabolic tumor volume assessed by whole-body (18)F-FDG-PET/CT. Gene expression profiling scores by the NanoString PanCancer IO360 panel were not conclusive in our patient population. ABSTRACT: Background: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted. Methods: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival. Results: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline (18)F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm(3) delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm(3). No significant associations were observed between baseline GEP scores and survival. Conclusion: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab. MDPI 2021-01-06 /pmc/articles/PMC7825041/ /pubmed/33418936 http://dx.doi.org/10.3390/cancers13020168 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Awada, Gil
Jansen, Yanina
Schwarze, Julia Katharina
Tijtgat, Jens
Hellinckx, Lennert
Gondry, Odrade
Vermeulen, Sim
Warren, Sarah
Schats, Kelly
van Dam, Pieter-Jan
Kockx, Mark
Keyaerts, Marleen
Everaert, Hendrik
Seremet, Teofila
Rogiers, Anne
Neyns, Bart
A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab
title A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab
title_full A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab
title_fullStr A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab
title_full_unstemmed A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab
title_short A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab
title_sort comprehensive analysis of baseline clinical characteristics and biomarkers associated with outcome in advanced melanoma patients treated with pembrolizumab
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825041/
https://www.ncbi.nlm.nih.gov/pubmed/33418936
http://dx.doi.org/10.3390/cancers13020168
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