Background: DMFS is an important endpoint for patients with stage III cutaneous melanoma, as delaying or preventing systemic disease is associated with improved clinical and patient-reported outcomes. Prior results from the phase 3 COMBI-AD trial (NCT01682083) showed 5-year DMFS rates of 65% with adjuvant D + T vs 54% with placebo (PBO; hazard ratio [HR] = 0.55; 95% CI: 0.44-0.70). An analysis of DMFS by AJCC-7 stages IIIA-C suggested a similar benefit of D + T vs PBO regardless of stage (Dummer R et al. N Engl J Med. 2020). Here, we report 5-year DMFS rates by AJCC-8 stages IIIA-D, other prognostic subgroups, and results of a regression tree analysis with DMFS. Methods: Patients with resected AJCC-7 stage III BRAF^V600E/K-mutant melanoma were randomized to either D (150 mg twice daily) + T (2 mg once daily) or 2 matched PBOs for 12 months. Primary endpoint was relapse-free survival (RFS); DMFS was a secondary endpoint. Kaplan-Meier survival analyses were performed to assess the long-term benefits for DMFS rates with D + T vs PBO. The regression tree analysis (data cutoff: 5 years) for all patients (N = 870) evaluated potential prognostic/predictive factors of long-term DMFS including baseline age, sex, region, BRAF mutation type, body mass index, lactate dehydrogenase levels, ECOG, T and N categories, histology, primary tumor ulceration, treatment type, number of lymph nodes with metastases, tumor mutational burden, and interferon-gamma gene expression signature (IFN-γ GES). Results: At 5 years, DMFS rates were higher for patients with AJCC-8 stages IIIB-D disease receiving adjuvant D + T vs PBO (table). Five-year DMFS rates also favored D + T vs PBO in subgroups of patients with microscopic or macroscopic lymph node involvement (table) and those with or without primary tumor ulceration and/or in-transit metastases. A regression tree revealed T and N stage, treatment type, and IFN-γ GES as important variables defining 5-year DMFS subgroups. Conclusions: In this retrospective analysis, adjuvant D + T provided long-term DMFS benefit vs PBO in stage IIIB-D patients with resected BRAF^V600E/K-mutant melanoma. Key clinical and patient factors impacting DMFS were similar to prior RFS findings (ESMO 2021; Robert C et al. Ann Oncol. 2021) and included T and N stage, treatment type, and IFN-γ GES. These results further validate the robust long-term clinical benefit of adjuvant D + T for patients with melanoma. Clinical trial information: NCT01682083.