Abstract 197: 5-year survival for patients with metastatic melanoma who had no evidence of disease at time of treatment with patient specific tumor stem cell vaccines
Authors: Dillman Robert O. , DePriest Carol , Ellis Robine , Leon Cristina de 
Published: May 2015

Autologous melanoma cells that are proliferating and self-renewing in cell culture, have the phenotypic and functional characteristics of tumor stem cells. Such cells are responsible for invasiveness and metastases. They express not only a variety of melanoma-associated antigens, but also unique neoantigens associated with other mutations. Therefore such cells should provide excellent polyvalent antigenic targets for patient-specific vaccines. In successive trials in metastatic melanoma: [1] 74 patients injected with irradiated proliferating autologous tumor cells (TC) had a 20.5 month median overall survival (OS) and 29% 5-year OS (Cancer Biother Radiopharm 2007), [2] 54 patients injected with autologous dendritic cells that had been loaded with antigen from autologous proliferating tumor cells (DC/TC) had a 54% 5-year OS; (Cancer Biother Radiopharm 2009), [3] in a randomized trial survival was better for 18 patients treated with DC/TC compared to 24 TC-treated patients (J Immunother 2012). In the current analysis we examined the long-term benefits of DC/TC and TC in the subset of patients who, although they had experienced documented metastatic disease, had no detectable metastatic disease by physical examination or radiographic imaging at the time of vaccine treatment. OS was calculated from date of enrollment at the time of initiating vaccine in the various trials. Log rank tests were used to compare survival curves. In order to minimize potential bias, the study was limited to patients who received granulocyte-macrophage colony stimulating factor (GM-CSF) or interferon gamma (IFN-g) as adjuvants, and who received at least the first 3 planned weekly injections. There were 33 patients treated with DC/TC and 37 treated with TC. Median follow up was greater than 5 years for both groups with 8 DC/TC and 5 TC patients censored alive before 5 years; no patients were lost to follow up. There were no obvious prognostic differences between the treatment cohorts in terms of age, gender, or previous sites of metastases. Survival was longer in patients who received DC/TC, median not reached at 60 months vs 32 months, and 5-year OS 73% vs 43% (p=0.015). The survival for the TC cohort is consistent with the 40% to 45% 5-year survival rates reported for similar patients treated with BCG, BCG plus allogeneic tumor cells or melanoma peptide antigen immunotherapy following surgical resection of stage IV metastatic disease (Morton ASCO 2007, Tagawa Cancer 2006). The 73% 5-year survival rate for DC/TC suggests that autologous DC/TC may represent a superior adjunctive immunotherapy in such patients. (NCI-V01-1646 and NCT00436930) Supported by the Hoag Hospital Foundation and the Cancer Biotherapy Research Group.

Citation Format: Robert O. Dillman, Carol DePriest, Robine Ellis, Cristina de Leon. 5-year survival for patients with metastatic melanoma who had no evidence of disease at time of treatment with patient specific tumor stem cell vaccines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 197. doi:10.1158/1538-7445.AM2014-197