915P - Biomarkers for clinical outcome of combined immunotherapy with granulocyte-macrophage colony-stimulating factor-tranduced allogeneic prostate cancer...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Prostate Cancer
Cancer Immunology and Immunotherapy
Presenter Winald Gerritsen
Authors W.R. Gerritsen1, S. Santegoets1, A. Stam1, K. Hege2, J. Versluis1, N. Sacks2, I. Lowy3, T. Harding2, A. van den Eertwegh1, T. De Gruijl1
  • 1Medical Oncology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 2Clinical Studies, Cell Genesys, san francisco/US
  • 3Clinical Studies, medarex, Bloomsbury/US

Abstract

In a phase-I dose escalation trial in patients (N = 28) with CRPC we showed that GVAX and ipilimumab had an acceptable safety profile (Lancet Oncology 2012). We observed tumor responses and prolonged survival. Patients had CRPC and were chemotherapy-naïve. They received bi-weekly GVAX for a 24 week period combined with monthly intravenous administrations of ipilimumab. Each cohort of 3 patients received an escalating dose of ipilimumab at 0·3, 1·0, 3·0 or 5·0 mg/kg. In an expansion cohort 16 patients were treated with GVAX and 3·0 mg/kg ipilimumab. Since the teratment can be accompanied by side-effects (colitis, hypophysitis), we looked for lymphoid and myeloid markers as well as antibody formation. We observed a significantly prolonged OS for patients with high pre-treatment frequencies of CD4 + CTLA-4 + , CD4 + PD-1 + , or differentiated CD8+ T cells, or low pre-treatment frequencies of differentiated CD4+ T cells or CD4 + CD25hiFoxP3+ regulatory T cells. In contrast, increased frequencies of granulocytic Myeloid-Derived Suppressor Cells and high pre-treatment frequencies of monocytic CD14 + HLA-DRlo/- MDSC were associated with reduced OS. Antibody formation against PSMA, NRP2, and PNPO was associated with prolonged survival and especially when multiple antibodies were detected.

Conclusions

Together these data provide an immune profile to predict clinical outcome; both pre-treatment CD4+ T-cells as well as antibody formation was associated with prolonged survival. These potentially biomarkers for patient selection should be validated in patients treated with ipilimumab.

Disclosure

W.R. Gerritsen: member of advisory board of BMS,

K. Hege: former employee of Cell Genesys,

N. Sacks: former employee of Cell Genesys,

I. Lowy: former employee of Medarex,

T. Harding: former emloyee of Cell Genesys,

A. van den Eertwegh: member advisory board BMS,

T. De Gruijl: educational grant from Cell Genesys.

All other authors have declared no conflicts of interest.