Purpose of review: Dual immune checkpoint inhibition with ipilimumab plus nivolumab is currently the most effective, but also by far the most toxic treatment for advanced melanoma. Therefore, other combination partners that also lead to high and long-lasting responses but cause fewer adverse events were explored.
Recent findings: Relatlimab, a LAG-3 blocking antibody, was investigated in combination with nivolumab in a phase 2/3 randomized double-blind trial (RELATIVITY-047) and could demonstrate significantly improved progression-free survival in treatment-naive advanced melanoma patients compared with nivolumab monotherapy. While the safety profile is more favorable than that of ipilimumab plus nivolumab, no significant survival benefit has yet been demonstrated with the new combination over nivolumab monotherapy. The approval of relatlimab plus nivolumab by both the Food and Drug Administration and the European Medicines Agency expands the arsenal of treatment options for melanoma but raises new questions in clinical practice and a re-evaluation of currently established treatment standards and sequences.
Keywords: Dual checkpoint inhibition; LAG-3 blocking antibody; Melanoma; Overcoming anti-PD-1 resistance; Relatlimab plus nivolumab; T-cell exhaustion.
© 2023. The Author(s).