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

Abstract

e21583 Background: Uveal melanoma (UM) is a rare cancer that often metastasizes to the liver leading to a very poor prognosis. A combination of a one-time treatment with isolated hepatic perfusion (IHP) with high dose melphalan, and systemic immune checkpoint blockade with ipilimumab (3mg/kg) and nivolumab (1mg/kg) was investigated in patients with metastatic UM in the SCANDIUM II trial. Monitoring of circulating tumor DNA (ctDNA) for detection of residual disease and recurrence is a promising strategy to evaluate treatment response and predict prognosis in UM. In this retrospective analysis we analyzed ctDNA in patients in the SCANDIUM II trial and correlated the results with radiological assessment and clinical outcome. Methods: We analyzed 128 plasma cell-free DNA samples from 18 patients. Samples were analyzed by droplet digital PCR (Oncobit™ PM) targeting GNA11 Q209L (n = 9), GNAQ Q209L (n = 3) or GNAQ Q209P (n = 5). Twelve patients that received treatment, had evaluable radiology, a confirmed mutational status and a baseline sample were included in the analysis (median 8 samples per patient, range 3-16). Results: 7 out of 12 (58%) patients were ctDNA positive (ctDNA+) at baseline and 6 out of 7 (86%) ctDNA+ patients at baseline showed ctDNA clearance after treatment initiation. Two patients were ctDNA- at all measured time points. Baseline ctDNA levels (mutant copies/mL plasma) were associated with larger tumor size (M1a vs M1b/M1c, p < 0.001) and were also correlated with baseline LDH levels (Pearson’s correlation, r = 0.73, p = 0.0013). There was a numerical predictive value of ctDNA status at baseline on overall survival (OS), although not statistically significant, and no effect on progression-free survival (PFS). However, having a ctDNA negative (ctDNA-) sample between 2-4 months after treatment was significantly associated with improved OS (p < 0.001) and PFS (p = 0.02). Conclusions: For patients with uveal melanoma liver metastases treated with isolated hepatic perfusion in combination with immune checkpoint blockade, having a negative ctDNA blood sample 2-4 months after treatment is associated with improved PFS and OS. This is a potentially novel predictive biomarker that needs further validation.