Immune checkpoint inhibitors in melanoma in the metastatic, neoadjuvant, and adjuvant setting

Immune checkpoint inhibitors (ICI) are now standards of care in metastatic melanoma. We highlight here the dramatic improvement that these drugs brought in the history of melanoma care.

The monoclonal antibody directed against cytotoxic T-lymphocyte-associated protein 4, ipilimumab, was approved in 2011. Antiprogramed death cell protein 1 antibodies, nivolumab and pembrolizumab, were developed afterward and approved in 2014, demonstrating an improved efficacy/safety ratio as compared with ipilimumab. The association of ipilimumab and nivolumab now appears as the most efficient immunotherapy but the toxicity of this regimen is a limitation. These drugs have also been evaluated in the adjuvant setting for patients with stage III or IV resected melanoma where they have shown a significant benefit in terms of relapse-free survival.

ICI-based immunotherapy radically modified melanoma management and now appear as the most efficient treatment for patients with metastatic melanoma with characterized by long-lasting cancer remissions, and a distinct spectrum of immune-related adverse events. Their efficacy is now also established in the adjuvant setting and they are now actively evaluated as neoadjuvant treatment with promising early results.Intensive translational work is ongoing to identify predictive biomarkers of efficacy and toxicity to improve ICI benefit/risk ratio.