Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

Abstract

Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional metastatic disease who underwent RLND with curative intent. In this retrospective study, 78 melanoma patients with regional lymph node metastasis who underwent RLND received autologous DCs loaded with gp100 and tyrosinase and were analyzed for functional tumor-specific T cell responses in skin-test infiltrating lymphocytes. The study shows that adjuvant DC vaccination in melanoma patients with regional lymph node metastasis is safe and induced functional tumor-specific T cell responses in 71% of the patients. The presence of functional tumor-specific T cells was correlated with a better 2-year overall survival (OS) rate. OS was significantly higher after adjuvant DC vaccination compared to 209 matched controls who underwent RLND without adjuvant DC vaccination, 63.6 mo vs. 31.0 mo (p = 0.018; hazard ratio 0.59; 95%CI 0.42-0.84). Five-year survival rate increased from 38% to 53% (p < 0.01). In summary, in melanoma patients with regional metastatic disease, who are at high risk for recurrence and metastatic disease after RLND, adjuvant DC vaccination is well tolerated. It induced functional tumor-specific immune responses in the majority of patients and these were related to clinical outcome. OS was significantly higher compared to matched controls. A randomized clinical trial is needed to prospectively validate the efficacy of DC vaccination in the adjuvant setting.

Keywords: adjuvant therapy; dendritic cell; immunotherapy; melanoma; vaccination.

Figures

Figure 1.

Functional tumor-specific T cells correlate with clinical outcome in stage III melanoma patients. Kaplan–Meier curve of patients with regional metastasized melanoma who received adjuvant dendritic cell vaccination after radical lymph node dissection according to the presence or absence of functional tumor-specific T cells in skin-test infiltrating lymphocytes. RLND, radical lymph node dissection.

Figure 2.

Overall survival after radical lymph node dissection with or without adjuvant treatment with dendritic cell vaccination in melanoma patients with regional metastasis. Co, control group; DC, dendritic cell vaccinated patients; RLND, radical lymph node dissection.

Figure 3.

Distant metastatic free survival after radical lymph node dissection with or without adjuvant treatment with dendritic cell vaccination in melanoma patients with regional metastasis. Co, control group; DC, dendritic cell vaccinated patients; RLND, radical lymph node dissection.