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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2066609 |
| _version_ | 1818049768607186944 |
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| author | Jessica C. Hassel Timo E. Schank Heiko Smetak Jasmin Mühlbauer Martin Salzmann Devayani Machiraju Christian Menzer Kristin Lang Laila König Matthias F. Haefner Ingrid Hülsmeyer Christian Kohler Rainer Spang Alexander Enk Jürgen Debus Philipp Beckhove |
| author_facet | Jessica C. Hassel Timo E. Schank Heiko Smetak Jasmin Mühlbauer Martin Salzmann Devayani Machiraju Christian Menzer Kristin Lang Laila König Matthias F. Haefner Ingrid Hülsmeyer Christian Kohler Rainer Spang Alexander Enk Jürgen Debus Philipp Beckhove |
| author_sort | Jessica C. Hassel |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T10:42:50Z |
| format | Article |
| id | doaj.art-5c11e7dab9974230b5dc3d9f87c8177f |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-10T10:42:50Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-5c11e7dab9974230b5dc3d9f87c8177f2022-12-22T01:52:15ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2066609Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA)Jessica C. Hassel0Timo E. Schank1Heiko Smetak2Jasmin Mühlbauer3Martin Salzmann4Devayani Machiraju5Christian Menzer6Kristin Lang7Laila König8Matthias F. Haefner9Ingrid Hülsmeyer10Christian Kohler11Rainer Spang12Alexander Enk13Jürgen Debus14Philipp Beckhove15Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyDepartment of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyRegensburg Center for Interventional Immunology, University Hospital Regensburg, Regensburg, GermanyRegensburg Center for Interventional Immunology, University Hospital Regensburg, Regensburg, GermanyDepartment of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyDepartment of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyDepartment of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyDepartment of Radiation Oncology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Radiation Oncology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Radiation Oncology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyStatistical Bioinformatics Department, Institute of Functional Genomics, University of Regensburg, Regensburg, GermanyStatistical Bioinformatics Department, Institute of Functional Genomics, University of Regensburg, Regensburg, GermanyDepartment of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg. GermanyDepartment of Radiation Oncology, University Hospital Heidelberg, Heidelberg, GermanyRegensburg Center for Interventional Immunology, University Hospital Regensburg, Regensburg, GermanyIn 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.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2066609Melanomabrain metastasesradiationimmune checkpoint inhibitorstreatment sequenceimmune monitoring |
| spellingShingle | Jessica C. Hassel Timo E. Schank Heiko Smetak Jasmin Mühlbauer Martin Salzmann Devayani Machiraju Christian Menzer Kristin Lang Laila König Matthias F. Haefner Ingrid Hülsmeyer Christian Kohler Rainer Spang Alexander Enk Jürgen Debus Philipp Beckhove Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA) OncoImmunology Melanoma brain metastases radiation immune checkpoint inhibitors treatment sequence immune monitoring |
| 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 | Melanoma brain metastases radiation immune checkpoint inhibitors treatment sequence immune monitoring |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2066609 |
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