Comparison of early versus late onset of cellular immunotherapy in glioblastoma multiforme WHO IV.

Abstract

e13531 Background: Glioblastoma multiforme (GBM WHO grade IV glioma) is an aggressive disease with an unfavorable prognosis. The current first line treatment comprises radical operation and radiotherapy combined with temozolomide chemotherapy (Stupp protocol). After failure of first-line therapy there is currently no effective therapy. Here we report that dendritic cell therapy prolongs the survival for patients with newly diagnosed GBM V. Preliminary results show that adding checkpoint blockade with Nivolumab may cause a secondary therapy response. Methods: After isolating monocytes from peripheral blood of n = 11 patients with stage IV GBM, who underwent primary surgery and first-line radio-chemotherapy and from n = 34 patients, who failed first line therapy MoDC were generated using standard protocols. In 5 patients checkpoint blockade with Nivolumab was added after failure of DC therapy. Results: With a median overall survival of 41 months there is a clear improvement of the overall survival in patients, who received DC therapy after having finished the Stupp-protocol. The 3- year-survival rate after primary diagnosis is 46% (n = 5) and 1 patient is still alive after 81 months. In this patient a secondary therapy response of 16 months could be induced by adding low dose Nivolumab (1mg/kg body weight) after failure of DC therapy. The median survival after onset of DC therapy in patients who failed first line standard therapy is 10 months. The 3-year overall survival rate is 9% (n = 3). In 4 patients therapy with Nivolumab was combined causing only a limiting effect on the survival (4 to 10 months). Conclusions: Dendritic-cell based immune therapy started immediately after primary standard therapy has a clear impact on the overall survival of patients with newly diagnosed GBM IV. Whereas the therapeutic effect for patients after failure of first-line therapy is limited. Nivolumab may cause secondary therapy response in certain patients.