Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA)
Hassel JC, Schank TE, Smetak H, Muhlbauer J, Salzmann M, Machiraju D, Menzer C, Lang K, Konig L, Haefner MF, Huelsmeyer I, Kohler C, Spang R, Enk A, Debus J, Beckhove P (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 11
Article Number: 2066609
Journal Issue: 1
DOI: 10.1080/2162402X.2022.2066609
Abstract
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.
Involved external institutions
Universitätsklinikum Heidelberg
Germany (DE)
Universität Regensburg
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
Germany (DE)
Universität Regensburg
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
How to cite
APA:
Hassel, J.C., Schank, T.E., Smetak, H., Muhlbauer, J., Salzmann, M., Machiraju, D.,... Beckhove, P. (2022). Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA). OncoImmunology, 11(1). https://dx.doi.org/10.1080/2162402X.2022.2066609
MLA:
Hassel, Jessica C., et al. "Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA)." OncoImmunology 11.1 (2022).
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