Abstract 3703: Randomized trial of autologous dendritic cell vs tumor cell vaccines in patients with metastatic melanoma

Abstract

Abstract Autologous proliferating tumor cells may represent tumor stem cells and/or early progenitor cells that are capable of establishing new sites of metastatic cancer, and may provide excellent antigenic targets for patient-specific vaccines. In successive trials in metastatic melanoma, 74 patients treated with irradiated proliferating autologous tumor cell vaccines (TC) had a median survival of 20.5 months (29% 5-yr survival), and 54 patients treated with autologous dendritic cell vaccines (DC), in which dendritic cells were loaded with antigen from autologous proliferating tumor cells, had a 50% 5-yr survival (Cancer Biother Radiopharm 2007, 2009). A randomized trial was initiated to determine whether there was a difference in the two approaches. Key eligibility criteria included a diagnosis of metastatic melanoma, successful establishment of a short-term cell line from resected metastatic tumor with expansion to 200 million proliferating tumor cells by the Hoag Cell Biology Laboratory, and the ability of patients to travel to Newport Beach, CA. There were no eligibility restrictions for types or numbers of prior therapies. Patients were stratified by whether they had measurable disease and by whether their most advanced stage had been regional or distant metastases, then randomized to receive either TC or DC injected s.c. with 500 micrograms of GM-CSF, weekly for 3 weeks and then monthly for five months. This was designed as a randomized phase III trial with 90% power to detect a 50% difference in survival by intent-to-treat analysis. In April 2011 Hoag Hospital advised that the Cell Biology Laboratory was to be closed for strategic and economic reasons, forcing discontinuation of the trial. 42 of a planned 200 patients were randomized, and all 42 received the assigned treatment. Because of the premature closure, an unplanned interim analysis was performed. There were no differences between the two arms in patient characteristics for 17 different variables including age, gender, measurable disease, location of metastases, LDH, and prior therapies. One patient in the DC arm experienced complete regression of multiple measurable soft-tissue metastases. With 21 patients deceased, survival is superior in the DC arm (HR=0.27 95% CI 0.098-0.729) with median survival not reached vs 15.9 months and 2-year survival rates 72% vs 30% (p=.007 Mantle-Cox log rank test, and p=.011 Breslow generalized Wilcoxon). This study establishes the importance of denditic cells in active specific immunotherapy, confirms an earlier study showing a high rate of long-term survival in patients with metastatic melanoma treated with such therapy, and shows that a patient-specific DC product is superior to a patient-specific TC product in death reduction. (NCT00436930) Supported by the Hoag Hospital Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3703. doi:1538-7445.AM2012-3703