Complete Response to Nivolumab‐Relatlimab Following Progression of Invasive Sinonasal Mucosal Melanoma on First‐Line Nivolumab‐Ipilimumab: A Case Report

BACKGROUND: Mucosal melanoma (MM) is a rare and aggressive subtype of melanoma with a notably worse prognosis than cutaneous melanoma (CM) due to its occult presentation and unique molecular profile. For advanced cases, immunotherapy has improved outcomes in recent years, although more significantly for CM. The recently approved combination of nivolumab and relatlimab has emerged as a promising option for advanced melanoma and a potential alternative to the well-established nivolumab-ipilimumab regimen. Due to the rarity of MM often limiting thorough evaluation in trials, there remains a lack of guidance regarding the most appropriate regimen for optimal patient outcomes. CASE: A 70-year-old male with T4aN0M0 sinonasal MM was initiated on neoadjuvant nivolumab-ipilimumab therapy; however, disease progression soon after rendered the tumor unresectable. Despite undergoing 4 cycles, metastatic progression ensued, necessitating a shift to nivolumab-relatlimab therapy. Following 8 cycles of nivolumab-relatlimab alongside radiation to metastatic sites, the patient achieved a complete response, with no signs of active disease. Unfortunately, during a seven-week treatment interruption due to suspected immune-related gastrointestinal toxicity requiring corticosteroids, routine PET-CT monitoring revealed findings suspicious for new metastasis. Despite one additional cycle of immunotherapy, the patient's functional status deteriorated. Although repeat imaging showed stable disease, the patient elected to transition to supportive care without further treatment. CONCLUSION: This case exemplifies the use of nivolumab-relatlimab in achieving a complete response in a patient with advanced sinonasal MM that progressed after nivolumab-ipilimumab. While further investigation is needed to clarify the comparative efficacy of existing combination immunotherapy options, this report highlights nivolumab-relatlimab as a promising option with a potentially favorable safety profile in this rare and aggressive melanoma subtype.