Tolerability and efficacy of chemosaturation in combination with systemic therapy for metastatic uveal melanoma

Abstract

Uveal melanoma is the most common primary intraocular malignancy in adults. Metastatic disease occurs in approximately 40%-50% of patients, the liver being the predominant site of metastasis (>90%). Treatment options include immune checkpoint inhibitors (ICIs), the bispecific fusion protein tebentafusp, and liver-directed therapies such as chemosaturation. Despite these available approaches, treatment remains a significant challenge, with a median overall survival of approximately 1 year. In our retrospective study, we investigated the efficacy and tolerability of administering systemic therapy within a defined time interval of ±40 days relative to the date of chemosaturation. Patients included had received either ICI or tebentafusp in close temporal proximity to chemosaturation between November 2023 and July 2024. Treatment efficacy was assessed based on radiologic imaging according to response evaluation criteria in solid tumors, and tolerability was evaluated based on documented adverse events. A total of 10 patients with hepatic metastatic UM could be included in the study. Seven patients received systemic therapy with ICI; three patients were treated with tebentafusp. Hepatic disease control was achieved in all patients. Partial response was observed in 7 of 10 patients, while 3 of 10 patients demonstrated stable disease. Chemosaturation was associated mainly with pancytopenia in 5 of 10 patients. Additionally, immune-related adverse events of common terminology criteria for adverse events grade I-III were observed. In summary, our findings suggest that administering systemic therapy within the defined interval around chemosaturation can achieve disease control with acceptable tolerability. To further evaluate this therapeutic approach, prospective controlled studies are warranted to assess efficacy and optimize patient safety.

Keywords: chemosaturation; immunecheckpoint inhibitors; liver metastases; metastatic uveal melanoma; tebentafusp.