Immunotherapy has greatly improved treatment for advanced melanoma, but liver metastases remain a major challenge. The liver can act as an “immune sink,” where special immune cells destroy the T cells that are supposed to fight cancer. This weakens the body’s overall immune response and makes liver tumors especially hard to treat.
In the CHOPIN trial for uveal (eye) melanoma, researchers combined a liver-directed treatment called percutaneous hepatic perfusion (PHP) using melphalan with systemic immunotherapy (ipilimumab and nivolumab). PHP delivers high-dose chemotherapy directly to the liver while filtering the drug from the blood to protect the rest of the body. The combination greatly improved progression-free survival and response rates compared to liver treatment alone, and modestly increased overall survival.
Based on these results, a new Phase 1b/2 trial is testing melphalan-PHP combined with Opdualag (nivolumab plus relatlimab) in patients with cutaneous melanoma that has spread to the liver. The goal is to see whether clearing the liver’s immune-suppressive environment can make immunotherapy more effective and potentially lead to long-term remission.