In a Dutch single-center phase II trial (CHOPIN) reported in The Lancet Oncology, van den Hoek et al found that the addition of nivolumab and ipilimumab to percutaneous hepatic perfusion improved progression-free survival in patients with metastatic uveal melanoma.
Study Details
Seventy-six eligible patients at Leiden University Medical Centre with unresectable liver-only or liver-dominant metastatic uveal melanoma were enrolled in the trial between December 2020 and November 2024. Patients were randomly assigned to receive two perfusions with melphalan (3 mg/kg; maximum = 220 mg) scheduled in weeks 1 and 7 with (n = 38) or without (n = 38) ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every 3 weeks in weeks 0, 3, 6, and 9 without maintenance therapy. The primary endpoint of the study was 1-year progression-free survival.
Key Findings
Median follow-up was 24.9 months (interquartile range = 15.4–36.0 months). Progression-free survival at 1 year was 54.7% (95% confidence interval [CI] = 36.8%–69.5%) with combination therapy vs 15.8% (95% CI = 5.8%–30.1%) with perfusion alone (adjusted hazard ratio [HR] = 0.34, 95% CI = 0.19–0.60, P = .0002).
Median progression-free survival was 12.8 months (95% CI = 9.2–15.4 months) in the combination group vs 8.3 months (95% CI = 6.0–9.6 months) in the perfusion group (adjusted HR = 0.34, 95% CI = 0.19–0.60, P = .0002).
Grade 3 or 4 treatment-related adverse events occurred in 82% of patients in the combination therapy group vs 41% of the perfusion group, with the difference reflecting a higher incidence of both perfusion-related events (71% vs 32%) and immunotherapy-related events (16% vs not applicable) in the combination group. The most common grade 3 or 4 adverse events in the combination group were thrombocytopenia (34%), leukopenia (26%), γ-glutamyl transferase increase (18%), and anemia (13%). One treatment-related death (due to triple M syndrome [myocarditis, myositis, and myasthenia gravis]) occurred in the combination group.
The investigators concluded: “Adding ipilimumab and nivolumab to percutaneous hepatic perfusion significantly improved progression-free survival, but with a higher rate of adverse events. The combination therapy offers a promising new treatment paradigm for patients with metastatic uveal melanoma. These results would ideally be validated in larger, multicenter randomized trials; however, conducting such studies is challenging due to the low incidence of uveal melanoma.”
Ellen Kapiteijn, MD, of the Department of Medical Oncology, Leiden University Medical Centre, Leiden, Netherlands, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Leiden University Medical Centre, Delcath Systems, and Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
