1. Tumour-informed liquid biopsies to monitor advanced melanoma patients under immune checkpoint inhibition.
- Author
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Schroeder C, Gatidis S, Kelemen O, Schütz L, Bonzheim I, Muyas F, Martus P, Admard J, Armeanu-Ebinger S, Gückel B, Küstner T, Garbe C, Flatz L, Pfannenberg C, Ossowski S, and Forschner A
- Subjects
- Humans, Liquid Biopsy methods, Male, Female, Middle Aged, Aged, Prospective Studies, Adult, Biomarkers, Tumor genetics, Positron Emission Tomography Computed Tomography methods, Aged, 80 and over, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, Immune Checkpoint Inhibitors therapeutic use, Circulating Tumor DNA genetics, Circulating Tumor DNA blood
- Abstract
Immune checkpoint inhibitors (ICI) have significantly improved overall survival in melanoma patients. However, 60% experience severe adverse events and early response markers are lacking. Circulating tumour DNA (ctDNA) is a promising biomarker for treatment-response and recurrence detection. The prospective PET/LIT study included 104 patients with palliative combined or adjuvant ICI. Tumour-informed sequencing panels to monitor 30 patient-specific variants were designed and 321 liquid biopsies of 87 patients sequenced. Mean sequencing depth after deduplication using UMIs was 6000x and the error rate of UMI-corrected reads was 2.47×10
-4 . Variant allele fractions correlated with PET/CT MTV (rho=0.69), S100 (rho=0.72), and LDH (rho=0.54). A decrease of allele fractions between T1 and T2 was associated with improved PFS and OS in the palliative cohort (p = 0.008 and p < 0.001). ctDNA was detected in 76.9% of adjuvant patients with relapse (n = 10/13), while all patients without progression (n = 9) remained ctDNA negative. Tumour-informed liquid biopsies are a reliable tool for monitoring treatment response and early relapse in melanoma patients with ICI., (© 2024. The Author(s).)- Published
- 2024
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