Multinational study of prognostic value of circulating tumor DNA in metastatic uveal melanoma

Although circulating tumor DNA (ctDNA) predicted overall survival (OS) in metastatic uveal melanoma (mUM) treated with tebetafusp, its broader prognostic value across treatment modalities remains unclear. A multinational study assessed the prognostic relevance of longitudinal ctDNA detection and mutant allele fraction (MAF) in mUM patients treated with different modalities. Using an IVDR-certified PCA assay targeting GNAQ^Q209 and GNA11^Q209 mutations, the authors analyzed 655 samples from 75 patients. Absence of detectable ctDNA in baseline samples prior to first-line therapy was associated with improved OS (HR 0.13; p=0.02) and progression-free survival (PFS; HR 0.31; p=0.008). Similar associations were observed in patients treated with any line of therapy (OS: HR 0.19, p=0.002; PFS: HR 0.27, p=0.02). Detection of ctDNA within 3 months of therapy initiation was associated with worse outcomes, independent of baseline detection. Furthermore, patients with MAF > 5% at any timepoint had a significantly poorer prognosis compared with patients with MAF , 5% (median OS 4 versus 21 months; p<0.001; median PFS 2.5 versus 3.6 months; p=0.004). The authors conclude that ctDNA is prognostic of patient outcome and enables therapy monitoring in mUM.