Real world experience of melphalan/hepatic delivery system with circulating tumor DNA (ctDNA) monitoring in patients with metastatic uveal melanoma.

Abstract

e21520 Background: Percutaneous hepatic perfusion (PHP) is a repeatable procedure that delivers melphalan loco-regionally with a hepatic delivery system (Melphalan/HDS), with subsequent extracorporeal blood filtration to achieve an improved therapeutic index. Melphalan/HDS has received FDA approval in patients with unresectable liver-dominant metastatic uveal melanoma (mUM). These results summarize real-world experience of Melphalan/HDS in mUM patients with ctDNA treatment monitoring. Methods: Between February to January 2025, the first 8 consecutive patients with unresectable mUM treated with Melphalan/HDS administered every 6-8 weeks were evaluated at the University of Wisconsin. Toxicity data, response rates, HLA-A*02:01 status, and ctDNA were obtained. Results: Average age was 60.6 years (range 38-74), 4 male and 4 female, and all ECOG 0-1. Two patients had prior ablation of liver lesions and 1 patient had prior systemic therapy. The number of liver lesions ranged from 5 to 100+, with average size of 2 cm (range 0.8-7 cm). Four patients had liver tumor occupancy ≥ 26%; none had extrahepatic disease. The 8 patients received 26 cycles of Melphalan/HDS (range 2-5). Grade 3/4 toxicities included thrombocytopenia (50%), anemia (25%) and neutropenia (13%). Grade 1/2 toxicities included fatigue (88%), anemia (50%), increased alkaline phosphate (38%), neutropenia (38%), thrombocytopenia (38%) and increased ALT (25%). Partial response was observed in 6 patients and stable disease in 2 patients. In 6 of these patients; serial ctDNA was analyzed. Three patients decreased to undetectable levels; one patient maintained an undetectable level. Two patients whose ctDNA did not become undetectable subsequently developed progressive disease. Conclusions: Melphalan/HDS is a novel treatment option for patients with unresectable mUM. In our real-world study, we observed good tolerability and encouraging efficacy. We did not observe any new safety signals. The treatment resulted in disease control for all patients, including 6 of 8 with an objective tumor response, irrespective of HLA-A*02:01 status. Monitoring of ctDNA as an indicator of efficacy in patients receiving Melphalan/HDS shows promise and merits further investigation. Patient HLA-A*02:01 status Liver Lesions Melphalan/HDS Treatments Response 60 yo Female Positive 100+ 3 SD 58 yo Male Negative 20+ 5 PR 65 yo Female Positive 20+ 4 PR 74 yo Male Negative 20+ 3 PR 70 yo Male Positive 10 3 PR 38 yo Male Positive 10 2 PR 52 yo Female Negative 5 5 PR 68 yo Female Negative 5 3 SD