Hassel, Jessica C. and Schank, Timo E. and Smetak, Heiko and Muhlbauer, Jasmin and Salzmann, Martin and Machiraju, Devayani and Menzer, Christian and Lang, Kristin and Konig, Laila and Haefner, Matthias F. and Huelsmeyer, Ingrid and Kohler, Christian and Spang, Rainer and Enk, Alexander and Debus, Juergen and Beckhove, Philipp (2022) Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA). ONCOIMMUNOLOGY, 11 (1): 2066609. ISSN 2162-402X,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; STEREOTACTIC RADIOSURGERY; COMBINED NIVOLUMAB; ACQUIRED-RESISTANCE; RADIOTHERAPY; IPILIMUMAB; CANCER; RADIATION; BLOCKADE; SURVIVAL; Melanoma; brain metastases; radiation; immune checkpoint inhibitors; treatment sequence; immune monitoring; biomarkers |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Feb 2024 15:08 |
| Last Modified: | 20 Feb 2024 15:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57678 |
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