Initial treatment of metastatic uveal melanoma

HLA: human leukocyte antigen; PHP: percutaneous hepatic perfusion; IHP: isolated hepatic perfusion; OS: overall survival; PFS: progression-free survival; PD-1: programmed cell death protein 1.

¶ Although PFS and objective response rates are modest in patients receiving tebentafusp, this agent improved OS in patients who are HLA-A*02:1 positive, including those whose best treatment response is progressive disease.

Δ Significant extrahepatic disease is defined as tumor burden outside the liver that is extensive enough to require treatment (eg, due to symptoms, tumor bulk, and/or rapidly progressive disease).

◊ Patients with liver-dominant disease may reasonably opt for systemic therapy over locoregional therapy, given the prognosis of this disease and limited data comparing these treatment approaches.

§ Patients who decline or are ineligible for combination nivolumab plus ipilimumab (eg, due to potential toxicity) may alternatively be offered single-agent immunotherapy with a PD-1 inhibitor. We do not typically use chemotherapy or MEK inhibitors due to limited efficacy. Those who are unable to tolerate systemic therapy may be offered best supportive care.

¥ The optimal liver-directed therapy is not known. Selection of therapy is based on clinician and institutional expertise. Most patients with both liver-dominant and limited extrahepatic disease may receive liver-directed therapy followed by systemic therapy. Systemic therapy can be initiated once liver-directed therapy has achieved some degree of hepatic disease control. Alternatively, select patients with low-volume, indolent metastases outside the liver (particularly within the lung) may be observed after completing liver-directed therapy.