Efficacy of combined targeted therapy and immunotherapy in BRAF-mutated patients with advanced melanoma and prognostic significance of lactate dehydrogen activity: Experience of a tertiary center

Background: To evaluate the efficacy of combined targeted therapy and immunotherapy in patients with BRAF-mutated melanoma, and to assess the prognostic significance of lactate dehydrogenase (LDH) activity. Methods: This retrospective study included 68 patients (mean age 57.4±13.6 years), with advanced melanoma treated at a tertiary centre between 2019 and 2024. Patients were divided into two groups: immunotherapy (nivolumab/pembrolizumab) and combined BRAF/ MEK-targeted therapy (dabrafenib/trametinib or vemurafenib/cobimetinib). Clinical outcomes were analysed according to LDH values. Results: Median progression-free survival (PFS) was 15.97 months, while median overall survival (OS) reached 38.57 months in our patient population. No statistically significant differences were observed between treatment groups, although numerically longer survival was noted in the immunotherapy group. Elevated LDH activity was detected in 41% of patients, more frequently among those receiving targeted therapy. Patients with normal LDH activity had significantly longer OS than those with elevated LDH (NR vs 16.6 months; p=0.009). Conclusion: Established prognostic value of LDH was firmed in our patient population. Patients with LDH activity within the reference range had significantly longer overall survival, underscoring LDH's importance as a routine biomarker in clinical practice. Immunotherapy showed numerically better outcomes than combined BRAF/MEK therapy, highlighting the need for further prospective studies to validate these findings.