Enhanced dacarbazine efficacy in advanced melanoma patients previously treated with immune checkpoint inhibitors in Korea.

e21528 Background: Immune checkpoint inhibitors (ICI) have revolutionized advanced malignant melanoma treatment. But the lack of effective options post-ICI failure presents a significant challenge. Despite its modest efficacy, chemotherapy with dacarbazine remains practical choice in metastatic melanoma patients after ICI failure. Researchers suggested an increased efficacy of chemotherapy in melanoma patients previously treated with ICI. In this study, we aimed to assess the efficacy of dacarbazine of patients with or without prior ICI treatment. Methods: 71 patients with histologically confirmed malignant melanoma, who diagnosed and underwent chemotherapy between 2011 and 2023 at the Kyungpook National University Chilgok Hospital (Daegu, Korea) were included in this retrospective study. We included patients who had received either dacarbazine single or CVD(Cisplatin, Vinblastine, Dacarbazine) regimen for an unresectable stage IIIC, IIID or IV acral, cutaneous, mucosal melanoma according to American Joint Committee on Cancer(AJCC) 8th edition. Results: Among a total of 71 individuals, there were 16 patients who had not previously received pembrolizumab treatment (DTI-only group). There were 55 patients in the pembrolizumab (pem-DTI group) experienced group. The median PFS was 2.3 months in the DTI-only group and 3.9 months in the pem-DTI group, reflecting a significant PFS difference of 1.6 months. And the median OS was 6.8 months in the DTI-only group and 19.0 months in the pem-DTI group, demonstrating a statistically significant difference. In the univariate and multivariate analysis for PFS, the use of pembrolizumab was advantageous compared to non-use (HR 0.246, 95% CI 0.106-0.576, p= 0.001). The only favorable condition in the univariate analysis for OS was the use of pembrolizumab compared to non-use (HR 0.198, 95% CI 0.068-0.574, p= 0.003). The mean duration of response for the DTI-only group was 4.64 months, while for the pem-DTI group, it was 8.11 months, indicating that the pem-DTI group exhibited a longer duration. Conclusions: We have demonstrated superior PFS and OS in the group of metastatic melanoma patients who received dacarbazine after prior treatment with pembrolizumab compared to those treated with dacarbazine alone. Dacarbazine may still be a valid option after failure of ICI +/- targeted treatment. Future studies should focus on the immunomodulatory effects of dacarbazine on the tumor microenvironment, which could be harnessed to potentially enhance sensitivity to immune checkpoint-based therapy.