Long-term survival in patients with metastatic melanoma vaccinated with melanoma-antigen loaded dendritic cells

Abstract

8547 Background: Previous clinical trials have demonstrated safety and tolerability of cancer antigen-loaded dendritic cells (DCs) in the treatment of metastatic melanoma. Further, DCs administered to patients with metastatic melanoma are immunogenic and induce durable clinical responses even in patients who failed previous cytotoxic therapy. This report is an analysis of long term clinical outcomes of DC vaccinated patients from our institution. Methods: Between March 1999 and February 2005 seventy patients with metastatic melanoma were treated with DC vaccines in four sequential phase I-IIa clinical trials. Most patients had M1b or M1c metastatic disease. DCs were generated either from CD34+ hematopoietic progenitors or from monocytes. Forty nine HLA-A*0201+ patients received vaccines pulsed with melanoma antigen derived peptides (MART-1, MAGE-3, TYR and gp100). Twenty one patients received DCs loaded with killed allogeneic melanoma cells. KLH was used as helper antigen and, in HLA-A*0201+ patients, Flu-Matrix peptide was used as control antigen. Patients received up to eight DC vaccinations over a maximum of 7 months. Results: DC vaccinations were safe and tolerable. Fifteen out of 70 (21%) patients are alive as of November 2006. The median survival in this group of surviving patients is 46 months (range 22–92 months). Three patients had no evidence of disease upon completion of DC vaccinations by clinical and positron emission tomography scanning. Four patients had experienced objective clinical responses by RECIST criteria (2 CRs and 2 PRs) based on clinical examination and computerized tomography or magnetic resonance imaging. These included two patients that had failed previous cytotoxic and cytokine therapy. Eight patients are alive with disease. Five of 15 long term survivors had no additional therapy other than DC vaccinations including a patient with CR of liver lesions who remains free of disease 80 months post DC vaccination. Conclusions: DC vaccines bring clinical benefit and elicit durable responses in a fraction of patients with metastatic melanoma. These vaccines may provide a survival advantage. Future studies are underway to improve DC vaccine efficacy for treatment of metastatic melanoma. No significant financial relationships to disclose.