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Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?
The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benef...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966631/ https://www.ncbi.nlm.nih.gov/pubmed/31817189 http://dx.doi.org/10.3390/cancers11121940 |
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author | Schouwenburg, Maartje G. Suijkerbuijk, Karijn P.M. Koornstra, Rutger H.T. Jochems, Anouk van Zeijl, Michiel C.T. van den Eertwegh, Alfons J.M. Haanen, John B.A.G. Aarts, Maureen J.B. van Akkooi, Alexander C.J. van den Berkmortel, Franchette W.P.J. de Groot, Jan Willem B. Hospers, Geke A.P. Kapiteijn, Ellen Kruit, Wim H. Piersma, Djura van Rijn, Rozemarijn S. ten Tije, Albert J. Vreugdenhil, Gerard van der Hoeven, Jacobus J.M. Wouters, Michel W.J.M. |
author_facet | Schouwenburg, Maartje G. Suijkerbuijk, Karijn P.M. Koornstra, Rutger H.T. Jochems, Anouk van Zeijl, Michiel C.T. van den Eertwegh, Alfons J.M. Haanen, John B.A.G. Aarts, Maureen J.B. van Akkooi, Alexander C.J. van den Berkmortel, Franchette W.P.J. de Groot, Jan Willem B. Hospers, Geke A.P. Kapiteijn, Ellen Kruit, Wim H. Piersma, Djura van Rijn, Rozemarijn S. ten Tije, Albert J. Vreugdenhil, Gerard van der Hoeven, Jacobus J.M. Wouters, Michel W.J.M. |
author_sort | Schouwenburg, Maartje G. |
collection | PubMed |
description | The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH. |
format | Online Article Text |
id | pubmed-6966631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69666312020-02-04 Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? Schouwenburg, Maartje G. Suijkerbuijk, Karijn P.M. Koornstra, Rutger H.T. Jochems, Anouk van Zeijl, Michiel C.T. van den Eertwegh, Alfons J.M. Haanen, John B.A.G. Aarts, Maureen J.B. van Akkooi, Alexander C.J. van den Berkmortel, Franchette W.P.J. de Groot, Jan Willem B. Hospers, Geke A.P. Kapiteijn, Ellen Kruit, Wim H. Piersma, Djura van Rijn, Rozemarijn S. ten Tije, Albert J. Vreugdenhil, Gerard van der Hoeven, Jacobus J.M. Wouters, Michel W.J.M. Cancers (Basel) Article The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH. MDPI 2019-12-04 /pmc/articles/PMC6966631/ /pubmed/31817189 http://dx.doi.org/10.3390/cancers11121940 Text en © 2019 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 Schouwenburg, Maartje G. Suijkerbuijk, Karijn P.M. Koornstra, Rutger H.T. Jochems, Anouk van Zeijl, Michiel C.T. van den Eertwegh, Alfons J.M. Haanen, John B.A.G. Aarts, Maureen J.B. van Akkooi, Alexander C.J. van den Berkmortel, Franchette W.P.J. de Groot, Jan Willem B. Hospers, Geke A.P. Kapiteijn, Ellen Kruit, Wim H. Piersma, Djura van Rijn, Rozemarijn S. ten Tije, Albert J. Vreugdenhil, Gerard van der Hoeven, Jacobus J.M. Wouters, Michel W.J.M. Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? |
title | Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? |
title_full | Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? |
title_fullStr | Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? |
title_full_unstemmed | Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? |
title_short | Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH? |
title_sort | switching to immune checkpoint inhibitors upon response to targeted therapy; the road to long-term survival in advanced melanoma patients with highly elevated serum ldh? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966631/ https://www.ncbi.nlm.nih.gov/pubmed/31817189 http://dx.doi.org/10.3390/cancers11121940 |
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