Tumour-informed liquid biopsies to monitor advanced melanoma patients under immune checkpoint inhibition

Christopher Schroeder, Sergios Gatidis, Olga Kelemen, Leon Schütz, Irina Bonzheim, Francesc Muyas, Peter Martus, Jakob Admard, Sorin Armeanu-Ebinger, Brigitte Gückel, Thomas Küstner, Claus Garbe, Lukas Flatz, Christina Pfannenberg, Stephan Ossowski and Andrea Forschner ()
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Christopher Schroeder: University of Tübingen
Sergios Gatidis: University Hospital Tübingen
Olga Kelemen: University of Tübingen
Leon Schütz: University of Tübingen
Irina Bonzheim: University Hospital Tübingen
Francesc Muyas: University of Tübingen
Peter Martus: Institute for Clinical Epidemiology and Applied Biostatistics (IKEaB)
Jakob Admard: University of Tübingen
Sorin Armeanu-Ebinger: University of Tübingen
Brigitte Gückel: University Hospital Tübingen
Thomas Küstner: University Hospital Tübingen
Claus Garbe: University Hospital Tübingen
Lukas Flatz: University Hospital Tübingen
Christina Pfannenberg: University Hospital Tübingen
Stephan Ossowski: University of Tübingen
Andrea Forschner: University Hospital Tübingen

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: 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

Date: 2024
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DOI: 10.1038/s41467-024-52923-0

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