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Nivolumab/relatlimab in advanced melanoma: a profile of its use

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Abstract

Nivolumab and relatlimab-rmbw (Opdualag; hereafter referred to as nivolumab/relatlimab) is a fixed dose combination of monoclonal antibodies for infusion, which expands the number of available therapies against advanced melanoma in patients aged ≥ 12 years. Dual checkpoint inhibition of programmed cell death protein-1 (PD-1) by nivolumab and lymphocyte-activation gene 3 (LAG-3) by relatlimab may stimulate an immune response against tumours. Notably, relatlimab is the first approved treatment targeting LAG-3. Nivolumab/relatlimab significantly decreased the risk of disease progression or death in comparison with nivolumab monotherapy during a phase 2/3 trial. The incidence of grade 3 or 4 adverse events was higher with nivolumab/relatlimab than with nivolumab monotherapy; however, no new safety signals were detected during the trial. As with other checkpoint inhibitors, immune-mediated reactions were reported with nivolumab/relatlimab treatment, which may be managed with treatment discontinuation or systemic immunosuppressants.

Plain Language Summary

Immune responses against cancer may become ineffective, in part due to the expression of inhibitory checkpoint receptors. Checkpoint inhibitors have been successfully used in the treatment of cancer by stimulating the immune system. However, not all patients respond to current treatment due to drug resistance. Nivolumab and relatlimab-rmbw (Opdualag; hereafter referred to as nivolumab/relatlimab) is approved for the treatment of advanced melanoma in patients aged ≥ 12 years. It contains two antibodies, with nivolumab targeting programmed cell death protein-1 and relatlimab targeting lymphocyte-activation gene 3 (LAG-3); both targets are inhibitory checkpoint receptors and relatlimab is the first approved treatment targeting LAG-3. In a clinical trial, nivolumab/relatlimab significantly decreased the risk of disease progression or death in comparison with nivolumab treatment alone. Adverse events of greater severity (i.e. grade 3 or 4) occurred more often in patients receiving nivolumab/relatlimab than nivolumab alone, although no new safety concerns were reported with nivolumab/relatlimab treatment. Reactions related to the immune system were managed by discontinuing treatment or with drugs that suppress the immune system. Nivolumab/relatlimab expands the number of available treatments for patients aged ≥ 12 years with advanced melanoma.

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Acknowledgements

The manuscript was reviewed by: D. Y. Reuben, Medical University of South Carolina College of Medicine, Charleston, SC, USA; R. Tripathi, Department of Molecular and Biomedical Pharmacology, University of Kentucky School of Medicine, Lexington, KY, USA. During the peer review process, Bristol-Myers Squibb Company, the marketing authorization holder of nivolumab/relatlimab, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Correspondence to Arnold Lee.

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A. Lee is a salaried employee of Adis International Ltd/Springer Nature and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Lee, A. Nivolumab/relatlimab in advanced melanoma: a profile of its use. Drugs Ther Perspect 39, 89–95 (2023). https://doi.org/10.1007/s40267-023-00980-8

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