OVER THE PAST decade, breakthroughs in cancer immunology have transformed the outlook for patients undergoing advanced melanoma therapy. Immune checkpoint inhibitors (ICIs) have become a cornerstone of treatment, harnessing the body’s immune system to target and destroy tumour cells. These innovations offer durable and, in some cases, long-lasting responses, significantly improving survival outcomes for people with metastatic or unresectable melanoma.
Combination Treatment Strengthens Advanced Melanoma Therapy
One of the most promising developments in advanced melanoma therapy is the combination of nivolumab plus relatlimab, which targets PD-1 and LAG-3 immune pathways. Findings from the RELATIVITY-047 trial showed that this dual ICI approach achieved superior results compared with nivolumab alone. Median progression-free survival was 10.2 months with the combination versus 4.6 months for nivolumab, while overall survival reached 51.0 months compared with 34.1 months. These improvements represent both statistically and clinically meaningful gains for patients.
Beyond traditional outcomes such as progression-free survival (PFS) and overall survival (OS), the study also evaluated treatment-free survival (TFS), the time patients remain off systemic therapy without progression or death. The nivolumab plus relatlimab combination extended TFS by an average of 2.9 months, meaning patients spent longer periods in remission and free from treatment-related side effects.
Redefining Success in Melanoma Immunotherapy
Crucially, most of the TFS period with the combination therapy was spent without severe toxicity, reflecting an improved quality of life. This highlights the value of patient-centred endpoints like TFS, which complement traditional clinical metrics and provide a clearer picture of real-world benefits.
As clinical research evolves, integrating TFS into trial design will help refine advanced melanoma therapy, guiding decisions on optimal treatment duration and sequencing. The sustained efficacy and tolerability of nivolumab plus relatlimab mark an important milestone in immunotherapy, signalling a more balanced and patient-focused approach to managing advanced melanoma.
Reference
Regan MM et al. Analysis of treatment-free survival of patients with advanced melanoma receiving nivolumab as monotherapy or in combination with relatlimab in RELATIVITY-047. J Immunother Cancer. 2025;13(9):e012747.
