Longitudinal ctDNA monitoring in patients with metastatic uveal melanoma undergoing isolated hepatic perfusion in combination with ipilimumab and nivolumab.

[BACKGROUND] Uveal melanoma (UM) is a rare cancer, which often metastasizes to the liver, leading to a poor prognosis. In the randomized SCANDIUM II trial, patients with metastatic UM received a one-time treatment with isolated hepatic perfusion using high-dose melphalan in combination with systemic immune checkpoint inhibition with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). In this study, we assessed circulating tumor DNA (ctDNA) in prospectively collected blood samples from all patients in the SCANDIUM II trial to detect residual disease and recurrence as a strategy to evaluate treatment efficacy and predict prognosis.

[PATIENTS AND METHODS] We analyzed ctDNA in 128 plasma samples from 18 patients using digital PCR (Oncobit™ PM) targeting GNA11 Q209L ( = 9), GNAQ Q209P ( = 5), or GNAQ Q209L ( = 4).

[RESULTS] At baseline, ctDNA was detectable in 9 of 17 (53%) patients, with levels positively correlated with lactate dehydrogenase and tumor burden. Analysis of ctDNA dynamics revealed ctDNA increase before progression in a subset of patients (5 of 12 patients, 42%). After treatment initiation, six of seven (86%) patients showed ctDNA clearance or decrease. Patients with undetectable ctDNA 2-4 months after the start of treatment had significantly improved progression-free survival ( = 0.024), and a non-significant improvement in overall survival.

[CONCLUSIONS] In patients with UM liver metastases treated with combined hepatic perfusion and immune checkpoint inhibition, ctDNA may serve as a predictive biomarker and warrants further validation.