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<h3>Background and Importance</h3> The rise of immunotherapy has transformed the management of melanoma, raising new medico-economic challenges. <h3>Aim and Objectives</h3> This study compares the costs of various therapeutic strategies according to disease stage, with the aim of optimising expenditures. <h3>Material and Methods</h3> This is a retrospective, single-centre study including patients who received an immunotherapy protocol for melanoma in 2024. Data were extracted from the Chimio software. Patients were divided into two groups: adjuvant treatment vs. metastatic treatment, and analysed based on the protocols used. <h3>Results</h3> In the adjuvant setting, 38 patients were treated (35 with Pembrolizumab 400 mg, 3 with Nivolumab 480 mg). Twelve patients were excluded due to ongoing treatment. Among patients receiving Pembrolizumab (n=23, median age: 73 years), the average number of cycles was 7.7, with a mean cost of €77,484 per patient. For those treated with Nivolumab (n=3, median age: 76 years), the average number of cycles was 12.3, with a cost of €66,037–representing a cost difference of €11,447 in favor of Nivolumab. In the metastatic setting, 7 patients received monotherapy. Patients treated with Pembrolizumab (n=5, median age: 86 years) received an average of 4 cycles (cost: €40,058), compared to 25 cycles for those on Nivolumab (n=2, median age: 93 years; cost: €133,863). Combination therapy was administered to 24 patients: 10 received Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg, followed by Nivolumab 480 mg (standard protocol; median age: 65 years; 3.1 induction cycles + 7.6 maintenance cycles; cost: €81,997). 14 received Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg, followed by Nivolumab 480 mg (inverted–dose protocol, for frail patients; median age: 80 years; 3.3 induction cycles + 10.4 maintenance cycles; cost: €79,406). <h3>Conclusion and Relevance</h3> Immunotherapy has significantly improved melanoma prognosis, albeit at high drug-related costs. In the adjuvant setting, our analysis highlights an average cost saving of €11,000 per patient when using Nivolumab instead of Pembrolizumab, with equivalent efficacy. This finding supports a review of prescribing practices in collaboration with clinicians. In the metastatic setting, the inverted-dose combination therapy appears to be better tolerated, with a lower cost, and remains a relevant cost-effective option for frail patients. For monotherapy, the difference in the average number of cycles per patient could not be explained. <h3>Conflict of Interest</h3> No conflict of interest