Immune checkpoint inhibitors have reshaped frontline treatment of metastatic melanoma. Still, many patients progress, and selecting and sequencing therapy afterward remains a major challenge. In this program, a panel of melanoma specialists from the United States and the United Kingdom looks at the evolving landscape after checkpoint inhibitor progression. They cover when to use BRAF/MEK inhibitors or keep them in reserve, why clinical trials matter, and how cellular therapy is changing practice. Faculty review tumor-infiltrating lymphocyte therapy alongside investigational PRAME-directed T-cell receptor therapy, bispecific T-cell engagers, and next-generation engineered products. They also explain how human leukocyte antigen restriction and PRAME expression shape eligibility. The conversation moves from patient selection and early referral to multidisciplinary workup and tumor harvest, then to toxicity management, insurance authorization, and quality of life. The panel closes with practical patient scenarios and future directions, emphasizing proactive testing, earlier referral, and strong communication between community oncologists and treatment centers.
Immune checkpoint inhibitors have transformed frontline care for metastatic melanoma, but a substantial proportion of patients do not achieve durable disease control, which leaves a clear unmet need after progression.
PRAME, a tumor-associated antigen highly expressed in melanoma with limited expression in healthy tissue, has become an increasingly attractive target for vaccines, engineered T-cell therapies, and bispecific agents
