Adjuvant DC-CIK plus high-dose interferon-α versus high-dose interferon-α alone in resected stage IIB–IIID melanoma: A propensity score–matched real-world study with long-term follow-up.

e21536 Background: High-dose interferon-α (HD-IFN) has historically served as a standard adjuvant therapy for resected stage IIB–IIID melanoma, yet relapse remains common. While dendritic cell-cytokine induced killer (DC-CIK) cell therapy has demonstrated antitumor activity across various malignancies, its specific efficacy in the adjuvant setting for melanoma remains unclear. We compared outcomes of DC-CIK plus HD-IFN versus HD-IFN alone in a real-world cohort. Methods: We retrospectively analyzed 903 patients with completely resected stage IIB–IIID melanoma between 2012 and 2016. Patients received either HD-IFN alone (20 MIU for 4 weeks, followed by 10 MIU for 11 months) or HD-IFN plus DC-CIK immunotherapy (at least 3 cycles). For DC-CIK preparation, an HLA-guided antigen loading strategy was employed. Autologous DCs were pulsed with peptides (MART-1/S-100) for HLA-A02/A24+ patients or tumor lysates for others and subsequently co-cultured with CIK cells to generate the effector product. Propensity score matching (1:1) was performed. Endpoints were recurrence-free survival (RFS), overall survival (OS), and toxicities. Results: After propensity score matching, a total of 586 patients were included in the final analysis, with 293 patients in each group. Baseline characteristics were well balanced between the two groups. The cohort comprised 209 patients with stage IIB-IIC disease (35.7%) and 377 patients with stage III disease (64.3%). With a median follow-up of 101.9 months, combination therapy significantly improved RFS compared with HD-IFN alone (median, 23.9 vs. 13.4 months; Hazard Ratio [HR], 0.67; 95% CI, 0.56–0.80; P<0.05). Although no significant difference in OS was observed in the overall population (median, 63.5 vs. 48.2 months; HR, 0.89; 95% CI, 0.72–1.10; P = 0.279), subgroup analysis revealed a significant OS benefit for stage III patients receiving combination therapy (median, 51.5 vs. 35.4 months; P = 0.033). Similarly, the combination group demonstrated superior median RFS in stage III disease (18.7 vs. 9.1 months; P < 0.01) and across specific subtypes, including acral (23.6 vs. 13.8 months; P < 0.01) and cutaneous melanoma (21.4 vs. 12.9 months; P < 0.05). Grade ≥3 adverse events occurred in 15.0% of the combination group and 12.5% of the monotherapy group, with no treatment-related deaths. Conclusions: DC-CIK combined with HD-IFN regimen was associated with significantly prolonged RFS compared with HD-IFN alone in resected stage IIB–IIID melanoma. Notably, this combination therapy demonstrated a significant OS benefit in patients with stage III disease, highlighting a high-risk subgroup that may derive the greatest survival advantage from this strategy. Prospective studies are warranted to confirm these findings and better define the role of DC-CIK–based adjuvant strategies.