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Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma

Background: Primary resistance to immunotherapy can be observed in approximately 40–65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma pa...

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Autores principales: Amaral, Teresa, Seeber, Olivia, Mersi, Edgar, Sanchez, Stephanie, Thomas, Ioannis, Meiwes, Andreas, Forschner, Andrea, Leiter, Ulrike, Eigentler, Thomas, Keim, Ulrike, Garbe, Claus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226601/
https://www.ncbi.nlm.nih.gov/pubmed/32331243
http://dx.doi.org/10.3390/cancers12041027
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author Amaral, Teresa
Seeber, Olivia
Mersi, Edgar
Sanchez, Stephanie
Thomas, Ioannis
Meiwes, Andreas
Forschner, Andrea
Leiter, Ulrike
Eigentler, Thomas
Keim, Ulrike
Garbe, Claus
author_facet Amaral, Teresa
Seeber, Olivia
Mersi, Edgar
Sanchez, Stephanie
Thomas, Ioannis
Meiwes, Andreas
Forschner, Andrea
Leiter, Ulrike
Eigentler, Thomas
Keim, Ulrike
Garbe, Claus
author_sort Amaral, Teresa
collection PubMed
description Background: Primary resistance to immunotherapy can be observed in approximately 40–65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma patients treated with first-line PD-1-based immunotherapy between January 2015 and December 2018 were investigated. Primary resistance was defined as progressive disease (PD) at the time of the first tumor assessment after starting immunotherapy. Patients with complete response, partial response, and stable disease were classified as having disease control (DC). Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier estimator. Univariate and multivariate logistic regression analyses were performed to determine prognostic factors associated with OS. Results: Three hundred and nineteen patients were included, and 40% had primary resistance to immunotherapy. The median follow-up time was 22 months. Patients with primary resistance had 1-, 2-, and 3-year OS rates of 41%, 15%, and 10%, respectively, compared to 91%, 81%, and 65% for the patients who achieved DC. The following independently significant prognostic factors for OS were identified: protein S100B level and primary tumor localization. There was a statistically significant difference for OS (p < 0.0001) but not for PFS (p = 0.230) when analyzing risk groups formed with a combination of these two variables (low-, intermediate-, and high-risk subgroups). Conclusions: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis. Response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors.
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spelling pubmed-72266012020-05-18 Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma Amaral, Teresa Seeber, Olivia Mersi, Edgar Sanchez, Stephanie Thomas, Ioannis Meiwes, Andreas Forschner, Andrea Leiter, Ulrike Eigentler, Thomas Keim, Ulrike Garbe, Claus Cancers (Basel) Article Background: Primary resistance to immunotherapy can be observed in approximately 40–65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma patients treated with first-line PD-1-based immunotherapy between January 2015 and December 2018 were investigated. Primary resistance was defined as progressive disease (PD) at the time of the first tumor assessment after starting immunotherapy. Patients with complete response, partial response, and stable disease were classified as having disease control (DC). Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier estimator. Univariate and multivariate logistic regression analyses were performed to determine prognostic factors associated with OS. Results: Three hundred and nineteen patients were included, and 40% had primary resistance to immunotherapy. The median follow-up time was 22 months. Patients with primary resistance had 1-, 2-, and 3-year OS rates of 41%, 15%, and 10%, respectively, compared to 91%, 81%, and 65% for the patients who achieved DC. The following independently significant prognostic factors for OS were identified: protein S100B level and primary tumor localization. There was a statistically significant difference for OS (p < 0.0001) but not for PFS (p = 0.230) when analyzing risk groups formed with a combination of these two variables (low-, intermediate-, and high-risk subgroups). Conclusions: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis. Response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors. MDPI 2020-04-22 /pmc/articles/PMC7226601/ /pubmed/32331243 http://dx.doi.org/10.3390/cancers12041027 Text en © 2020 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
Amaral, Teresa
Seeber, Olivia
Mersi, Edgar
Sanchez, Stephanie
Thomas, Ioannis
Meiwes, Andreas
Forschner, Andrea
Leiter, Ulrike
Eigentler, Thomas
Keim, Ulrike
Garbe, Claus
Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
title Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
title_full Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
title_fullStr Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
title_full_unstemmed Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
title_short Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
title_sort primary resistance to pd-1-based immunotherapy—a study in 319 patients with stage iv melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226601/
https://www.ncbi.nlm.nih.gov/pubmed/32331243
http://dx.doi.org/10.3390/cancers12041027
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