Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

Background:Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival.Methods:We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival.Results:Overall 5-year relative survival was 96.1% (95% CI 95.1–97.1%), being significantly lower in tumours of borderline (90.2%, 87.2–92.7%) than benign behaviour (97.4%, 96.3–98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%).Conclusion:The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

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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

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