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ASCO 2025: Modern Approaches to Metastatic Melanoma: Navigating the Treatment Landscape - Episode 2

Choosing a Preferred Combination Immune Checkpoint Inhibitor (ICI) Regimen and Identifying Patients Appropriate for ICI Monotherapy

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Panelists discuss frontline treatment preferences for metastatic melanoma, emphasizing the durability of combination immunotherapies like nivolumab plus ipilimumab, the emerging role of nivolumab plus relatlimab, and the importance of tailoring therapy based on disease characteristics, toxicity profiles, and individual patient factors.

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In this segment of the OncLive Peer Exchange discussion on metastatic melanoma, panelists dive deeper into their frontline treatment preferences. One expert expresses a strong preference for nivolumab plus ipilimumab, citing long-term survival data from the CheckMate 067 study, particularly for patients with aggressive or central nervous system–involved disease. However, they acknowledge that nivolumab plus relatlimab is an emerging option and may shift practices as more data become available. When it comes to anti–PD-1 monotherapy, this is now largely reserved for patients with contraindications to combination therapy—such as those with autoimmune diseases or transplants—due to its reduced toxicity profile.

Other experts weigh in with similar perspectives, reinforcing the long-standing confidence in nivolumab plus ipilimumab for its durability of response but also expressing interest in ongoing trials such as the Harmony trial , which pits relatlimab-nivolumab against newer checkpoint inhibitor combinations. One contributor highlights a nuanced perspective based on subset analyses: For patients in certain metastatic classifications (like M1a or M1b), anti–PD-1 monotherapy may be sufficient, as data suggest little additional benefit from adding a second agent. Additionally, sequential therapy (starting with monotherapy and adding later if needed) could achieve similar outcomes while minimizing toxicity.

The conversation closes with consideration of patient-specific factors in choosing monotherapy. Some clinicians prefer this approach in older patients or those with limited disease, such as lung-only metastases. One expert also mentions considering BRAF wild-type status as a factor based on earlier subset data suggesting more pronounced benefits from combination therapy in BRAF-mutant patients. All agree that although newer combinations offer promise, they still carry more toxicity than monotherapy, especially in vulnerable populations, and careful patient selection remains key.

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