Clinical outcomes and safety profile of dendritic cell–based vaccination in melanoma: Meta-analysis of reconstructed time to event data.

Abstract

e14597 Background: Dendritic cell (DC) vaccination has been investigated as adjuvant immunotherapy for melanoma; however, results from randomized trials remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of DC vaccines on survival outcomes and safety in patients with completely resected advanced melanoma. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials comparing adding DC-based vaccines vs standard treatment in patients with completely resected stage III/IV melanoma.The hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled for recurrence- free survival (RFS) and overall survival (OS) using a random-effects on R software version 4.3.1. When HRs were not directly reported, Kaplan–Meier curves were digitized to reconstruct individual time-to-event data, allowing pooled Kaplan–Meier estimation and log-rank testing. Results: Four trials (three phase II and one phase III), comprising 397 patients, met the eligibility criteria. DC vaccination was not associated with a statistically significant OS benefit compared with control (HR 0.70; 95% CI 0.30–1.63; p = 0.13; I² = 46.7%). Similarly, no significant difference was identified for RFS (HR 0.99; 95% CI 0.70–1.42; p = 0.21; I² = 31.3%). Pooled Kaplan–Meier curves reconstructed from published plots showed substantial overlap between groups for both RFS (log-rank 2p = 0.7) and OS (log-rank 2p = 0.8), with diminishing precision at later timepoints as the numbers at risk declined (at 60 months: RFS 1 vs 1; OS 1 vs 3 for vaccine vs control). Reconstruction fidelity was acceptable across studies (RMSE ~0.003–0.030; Kolmogorov–Smirnov p-values generally > 0.05). Severe toxicity was similar between arms (grade ≥3 adverse events: (OR 0.81; 95% CI 0.44 –1.47; p = 0.67; I² = 0%), and injection-site reactions did not differ significantly (OR 1.21; 95% CI 0.67–2.17; p = 0.45; I² = 0%). Conclusions: In patients with completely resected stage III/IV melanoma, current randomized evidence is insufficient to establish a survival benefit with DC vaccination, while severe toxicity rates appear similar to control. Larger, adequately powered randomized trials are required to define the clinical role and optimal strategies for DC-based vaccination.