Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA). (31st December 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Oncoimmunology. Volume 11:Number 1(2022)
• Publication Date: 2022-12-31
• Subjects: Melanoma -- brain metastases -- radiation -- immune checkpoint inhibitors -- treatment sequence -- immune monitoring -- biomarkers; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2022.2066609
• Languages: English
• ISSNs: 2162-402X

Abstract

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.