Immune biomarker evaluation of sequential tyrosine kinase inhibitor and nivolumab monotherapies in renal cell carcinoma: the phase I TRIBE trial.
Autor: | Shohdy KS; The Christie NHS Foundation Trust, Manchester, UK.; Division of Cancer Sciences, The University of Manchester, Manchester, UK., Pillai M; The Christie NHS Foundation Trust, Manchester, UK., Abbas KS; Faculty of Medicine, Alexandria University, Alexandria, Egypt., Allison J; The Christie NHS Foundation Trust, Manchester, UK., Waddell T; The Christie NHS Foundation Trust, Manchester, UK., Darlington E; The Christie NHS Foundation Trust, Manchester, UK., Mohammad S; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Hood S; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Atkinson S; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Simpson K; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Morgan D; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Nathan P; Mount Vernon Cancer Centre - East and North Herts NHS Trust, Northwood, Middlesex, UK., Kilgour E; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Dive C; Cancer Biomarker Centre, Cancer Research UK Manchester Institute, Manchester, UK., Thistlethwaite F; The Christie NHS Foundation Trust, Manchester, UK.; Division of Cancer Sciences, The University of Manchester, Manchester, UK. |
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Jazyk: | angličtina |
Zdroj: | Immuno-oncology technology [Immunooncol Technol] 2024 Mar 18; Vol. 22, pp. 100712. Date of Electronic Publication: 2024 Mar 18 (Print Publication: 2024). |
DOI: | 10.1016/j.iotech.2024.100712 |
Abstrakt: | Background: Predictive biomarkers for immune checkpoint blockade in the second-line treatment of metastatic renal cell carcinoma (mRCC) are lacking. Materials and Methods: Patients with histologically confirmed RCC who started nivolumab after at least 4 months of tyrosine kinase inhibitors (TKIs) were recruited for this study. Serial tissue and blood samples were collected for immune biomarker evaluation. The primary endpoint was to determine the association of specific T-cell subsets with clinical outcomes tested using Wilcoxon rank sum for clinical benefit rate (CBR) and log-rank test for progression-free survival (PFS). Results: Twenty patients were included in this trial with a median age of 64 years and followed-up for a median of 12 months. The median PFS for patients who received TKI was 13.8 months, while for those subsequently treated with nivolumab following TKI therapy, the median PFS was 2.6 months. CBR of nivolumab was 20% with two partial responses. Functionally active programmed cell death protein 1+ CD4+ T cells were enriched in non-responders ( q = 0.003) and associated with worse PFS on nivolumab ( P = 0.04). Responders showed a significant reduction in the effector CD4+T-cell (T Conclusions: In this small study, analysis of tissue-based and peripheral blood immune cell subsets predicted clinical outcomes of nivolumab. Further studies are warranted with larger populations to validate these observations. (© 2024 The Authors.) |
Databáze: | MEDLINE |
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