The first line treatment for Glioblastoma Multiforme (GBM), surgery, chemo-, and radiotherapy, gains patients little over one year. This makes novel treatment strategies highly warranted. One such strategy is cancer immune therapy (CIT). We conduct a randomised phase II clinical trial using a completely individualised CIT concept based on dendritic cells (DC) for the treatment of GBM. The novel feature of our DC-CIT technology is that exposure to bacterial endotoxins enables DC to prime type 1 T-helper cells, which support cytolytic anti-tumour immune responses. Such DC cancer vaccines have so far been investigated only in pilot trials. This randomised study aims at delivering safety as well as for the first time efficacy data. All patients aged 18-70 years receive standard first line therapy; in the randomised treatment group the DC-CIT is applied as add-on. The DC-CIT is inoculated into inguinal lymph nodes: after 6 weeks of chemoradiotherapy, 4 weekly applications; accompanying the maintenance chemotherapy 6 more applications every 4 weeks; finally 1 boost immunisation every 3 month as long as DC-CIT is available. We also include patients <18 and >70 in order to demonstrate safety and feasibility. Paediatric and elderly patients, however, are not randomised and are not evaluated together with patients 18-70. Primary and secondary objectives are progression free survival (PFS) and overall survival (OS). Here we present data from a first interim analysis; about 100 patients were recruited for the study, so far about one third of patients may be evaluated for overall survival.

As reported for other CIT trials, DC-CIT treatment shows no improvement in PFS, whereas OS is clearly prolonged. The mean±SD for PFS and OS is 243±167 (n=22) and 453±180 days (n=11) in the treatment group; and 226±170 (n=21) and 361±191 days (n=17) in the control group. At 12 months, 21/33 (73%) patients in the treatment group and 17/35 (48%) patients in the control group were still alive. At 18 months, 8/15 (50%) patients in the treatment and 6/18 (33%) patients in the control group were still alive. The treatment is well tolerated; no serious adverse events were noted that could clearly be attributed to DC-CIT. Inoculation into inguinal lymph nodes causes local swelling, redness, and tenderness; some of the patients develop fever of around 40°C. Although these are early data, we may already conclude that the DC-CIT treatment is very well tolerated. The trend in our observations suggest a good chance for establishing an overall survival benefit for GBM patients when DC-CIT is applied as an add-on treatment to the standard therapy in GBM.

Citation Format: Thomas Felzmann, Johanna Buchroithner, Christine Marosi, Martha Nowosielsky, Stefan Oberndorfer, Reinhard Ruckser, Karl Rössler, Amedeo Azizi, Gord von Campe, Karin Bordihn, The Austrian GBM-Vax Consortium. First interim analysis of a randomized study to evaluate safety and efficacy of individualized dendritic cell-based cancer immune therapy for glioblastoma multiforme. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4658. doi:10.1158/1538-7445.AM2013-4658