Treatments for metastatic uveal melanoma utilize various liver-directed strategies, yet optimal integration with systemic therapy is unclear. Here we examine recent evidence indicating that combining percutaneous hepatic perfusion with immune-checkpoint inhibitors might improve patient outcomes, compare it with data from other trials and highlight key questions around patient selection, sequencing and mechanisms that will shape future strategies.
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References
van den Hoek, L. et al. Percutaneous hepatic perfusion combined with ipilimumab and nivolumab for metastatic uveal melanoma (CHOPIN): a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 27, 372–382 (2026).
Zager, J. S. et al. Efficacy and safety of the melphalan/hepatic delivery system in patients with unresectable metastatic uveal melanoma: results from an open-label, single-arm, multicenter phase 3 study. Ann. Surg. Oncol. 31, 5340–5351 (2024).
Bagge, R. O. et al. Isolated hepatic perfusion with melphalan for patients with isolated uveal melanoma liver metastases: a multicenter, randomized, open-label, phase III trial (the SCANDIUM trial). J. Clin. Oncol. 41, 3042–3050 (2023).
Olofsson Bagge, R. et al. A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma metastases (SCANDIUM II trial). ESMO Open 9, 103623 (2024).
Piulats, J. M. et al. Nivolumab plus ipilimumab for treatment-naïve metastatic uveal melanoma: an open-label, multicenter, phase II trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J. Clin. Oncol. 39, 586–598 (2021).
Pelster, M. S. et al. Nivolumab and ipilimumab in metastatic uveal melanoma: results from a single-arm phase II study. J. Clin. Oncol. 39, 599–607 (2021).
Hassel, J. C. et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N. Engl. J. Med. 389, 2256–2266 (2023).
Carvajal, R. D. et al. Advances in the clinical management of uveal melanoma. Nat. Rev. Clin. Oncol. 20, 99–115 (2023).
Dudek-Perić, A. M. et al. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin. Cancer Res. 75, 1603–1614 (2015).
Ariyan, C. E. et al. Robust antitumor responses result from local chemotherapy and CTLA-4 blockade. Cancer Immunol. Res. 6, 189–200 (2018).
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S.A.K. has had consulting roles for Delcath, Ideaya, Immunocore, Regeneron and Replimune. R.D.C. has had consulting roles for Caper Labs, Castle Biosciences, Delcath, Ideaya, Immunocore, iOnctura, Mural Oncology, Pierre Fabre and Trisalus.
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NCT06519266: https://clinicaltrials.gov/study/NCT06519266
NCT06626516: https://clinicaltrials.gov/study/NCT06626516
NCT06627244: https://clinicaltrials.gov/study/NCT06627244
NCT07276386: https://clinicaltrials.gov/study/NCT07276386
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Khan, S.A., Carvajal, R.D. Synergistic integration of regional and systemic therapies in uveal melanoma. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01155-w
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DOI: https://doi.org/10.1038/s41571-026-01155-w
