OS2.5 Long term remission/survival over 8 years in patients with newly diagnosed glioblastoma (GBM) treated with ICT-107 dendritic cell-based immunotherapy (phase I)

Abstract

Background:We previously reported 7 patients with prolonged survival > 5 years from a phase I study of 16 newly diagnosed GBM patients (Neuro-Oncology 15(suppl3), 71, IT-015, 2013) and expression of four ICT-107 targeted antigens in pre-vaccine tumors correlated with prolonged OS and PFS in GBM patients (Cancer Immunol Immunother. 2013 Jan;62(1):125–35.Patients and Methods:ICT-107 is an autologous dendritic cell-based immunotherapy consisting of patient dendritic cells pulsed with six TAA peptides from AIM-2, TRP-2, HER2/neu, IL-13Ra2 (overexpressed on cancer stem cell), gp100, MAGE1 administered intradermal three times at two week intervals to HLA-A1 and/or HLA-A2 positive GBM patients after a standard therapy with concurrent Temozolomide and radiation therapy.Results:With a long term follow up, we identified 3(19%) of 16 the GBM patients were disease free over 8 years (PFS 9.1+, 8.5+, 8+) and 6 (38%) patients (5 males, 1 female, KPS 90%, age range 34–62 years old at age of diagnosis) >6 years (range 6.1- 9 years). There were 2 HLA-A1+ and 4 HLA-A2+ and their TAA expressed at least 5 peptides including antigens overexpressed on CSC in this group. One patient with PFS >9 years is working full time with good quality of life, showed immune response 2.5 (>1.5 fold increase IFNg production after vaccination by tetramer/FACS). Six (38%) of 16 GBM patients are presently alive at 9.4+, 9.1+, 8.5+, 8+, 7.9+ and 7.5+ years and only one patient received active treatment for recurrence. While long term remission and survival was seen in this 16 GBM patient cohort, median PFS was 16.9 months, 5-year PFS was 37.5% (95%:15.4–109), median OS was 38.4 months and 5-year OS rate was 50% (95% CI: 24.5–112).Conclusion:This is a first report of long term remission (19% of this group) > 8 years in newly diagnosed GBM from dendritic cell-based immunotherapy and 38% are alive >7.5 years). This correlated with cancer-stem-associated TAA expression, and a trend toward greater CD8 T cell cytokine responses.