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Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA)
In patients with melanoma brain metastases (MBM), a combination of radiotherapy (RT) with immune checkpoint inhibitors (ICI) is routinely used. However, the best sequence of radio-immunotherapy (RIT) remains unclear. In an exploratory phase 2 trial, MBM patients received RT (stereotactic or whole-br...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037491/ https://www.ncbi.nlm.nih.gov/pubmed/35481285 http://dx.doi.org/10.1080/2162402X.2022.2066609 |
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author | Hassel, Jessica C. Schank, Timo E. Smetak, Heiko Mühlbauer, Jasmin Salzmann, Martin Machiraju, Devayani Menzer, Christian Lang, Kristin König, Laila Haefner, Matthias F. Hülsmeyer, Ingrid Kohler, Christian Spang, Rainer Enk, Alexander Debus, Jürgen Beckhove, Philipp |
author_facet | Hassel, Jessica C. Schank, Timo E. Smetak, Heiko Mühlbauer, Jasmin Salzmann, Martin Machiraju, Devayani Menzer, Christian Lang, Kristin König, Laila Haefner, Matthias F. Hülsmeyer, Ingrid Kohler, Christian Spang, Rainer Enk, Alexander Debus, Jürgen Beckhove, Philipp |
author_sort | Hassel, Jessica C. |
collection | PubMed |
description | In patients with melanoma brain metastases (MBM), a combination of radiotherapy (RT) with immune checkpoint inhibitors (ICI) is routinely used. However, the best sequence of radio-immunotherapy (RIT) remains unclear. In an exploratory phase 2 trial, MBM patients received RT (stereotactic or whole-brain radiotherapy depending on the number of MBM) combined with ipilimumab (ipi) ± nivolumab (nivo) in different sequencing (Rad-ICI or ICI-Rad). Comparators arms included patients treated with ipi-free systemic treatment or without RT (in MBM-free patients). The primary endpoints were radiological and immunological responses in the peripheral blood. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Of 106 screened, 92 patients were included in the study. Multivariate analysis revealed an advantage for patients starting with RT (Rad-ICI) for overall response rate (RR: p = .007; HR: 7.88 (95%CI: 1.76–35.27)) and disease control rate (DCR: p = .036; HR: 6.26 (95%CI: 1.13–34.71)) with a trend for a better PFS (p = .162; HR: 1.64 (95%CI: 0.8–3.3)). After RT plus two cycles of ipi-based ICI in both RIT sequences, increased frequencies of activated CD4, CD8 T cells and an increase in melanoma-specific T cell responses were observed in the peripheral blood. Lasso regression analysis revealed a significant clinical benefit for patients treated with Rad-ICI sequence and immunological features, including high frequencies of memory T cells and activated CD8 T cells in the blood. This study supports increasing evidence that sequencing RT followed by ICI treatment may have better effects on the immunological responses and clinical outcomes in MBM patients. |
format | Online Article Text |
id | pubmed-9037491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-90374912022-04-26 Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) Hassel, Jessica C. Schank, Timo E. Smetak, Heiko Mühlbauer, Jasmin Salzmann, Martin Machiraju, Devayani Menzer, Christian Lang, Kristin König, Laila Haefner, Matthias F. Hülsmeyer, Ingrid Kohler, Christian Spang, Rainer Enk, Alexander Debus, Jürgen Beckhove, Philipp Oncoimmunology Original Research In patients with melanoma brain metastases (MBM), a combination of radiotherapy (RT) with immune checkpoint inhibitors (ICI) is routinely used. However, the best sequence of radio-immunotherapy (RIT) remains unclear. In an exploratory phase 2 trial, MBM patients received RT (stereotactic or whole-brain radiotherapy depending on the number of MBM) combined with ipilimumab (ipi) ± nivolumab (nivo) in different sequencing (Rad-ICI or ICI-Rad). Comparators arms included patients treated with ipi-free systemic treatment or without RT (in MBM-free patients). The primary endpoints were radiological and immunological responses in the peripheral blood. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Of 106 screened, 92 patients were included in the study. Multivariate analysis revealed an advantage for patients starting with RT (Rad-ICI) for overall response rate (RR: p = .007; HR: 7.88 (95%CI: 1.76–35.27)) and disease control rate (DCR: p = .036; HR: 6.26 (95%CI: 1.13–34.71)) with a trend for a better PFS (p = .162; HR: 1.64 (95%CI: 0.8–3.3)). After RT plus two cycles of ipi-based ICI in both RIT sequences, increased frequencies of activated CD4, CD8 T cells and an increase in melanoma-specific T cell responses were observed in the peripheral blood. Lasso regression analysis revealed a significant clinical benefit for patients treated with Rad-ICI sequence and immunological features, including high frequencies of memory T cells and activated CD8 T cells in the blood. This study supports increasing evidence that sequencing RT followed by ICI treatment may have better effects on the immunological responses and clinical outcomes in MBM patients. Taylor & Francis 2022-04-16 /pmc/articles/PMC9037491/ /pubmed/35481285 http://dx.doi.org/10.1080/2162402X.2022.2066609 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Hassel, Jessica C. Schank, Timo E. Smetak, Heiko Mühlbauer, Jasmin Salzmann, Martin Machiraju, Devayani Menzer, Christian Lang, Kristin König, Laila Haefner, Matthias F. Hülsmeyer, Ingrid Kohler, Christian Spang, Rainer Enk, Alexander Debus, Jürgen Beckhove, Philipp Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) |
title | Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) |
title_full | Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) |
title_fullStr | Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) |
title_full_unstemmed | Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) |
title_short | Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) |
title_sort | evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (elektra) |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037491/ https://www.ncbi.nlm.nih.gov/pubmed/35481285 http://dx.doi.org/10.1080/2162402X.2022.2066609 |
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