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60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

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DC-based immunotherapy for relapsed high grade glioma: clinical update of cohort A, B, C and D from the cohort comparison trial HGG-immuno-2003

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  • S. de Vleeschouwer - Department of Neurosurgery, University Hospital Leuven, Belgium
  • H. Ardon - Department of Neurosurgery, University Hospital Leuven, Belgium
  • S. Fieuws - Biostatistical Centre, Catholic University Leuven, Belgium
  • F. van Calenbergh - Department of Neurosurgery, University Hospital Leuven, Belgium
  • J. Goffin - Department of Neurosurgery, University Hospital Leuven, Belgium
  • J. van Loon - Department of Neurosurgery, University Hospital Leuven, Belgium
  • S. van Gool - Department of Pediatric Oncology, University Hospital Leuven, Belgium

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocMI.09-01

doi: 10.3205/09dgnc230, urn:nbn:de:0183-09dgnc2301

Published: May 20, 2009

© 2009 de Vleeschouwer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: The prognosis of patients with high-grade glioma (HGG) is dismal. We investigate the therapeutic role of vaccination with mature dendritic cells (DC) loaded with tumor lysates derived from resected tumor at the time of a relapse.

Methods: Dendritis cells were injected intradermally according to 3 different vaccination schedules (cohort A, B, C). Cohort D consisted of cohort C with the addition of local application of Imiquimod. Adverse events were registered and scored according to the National Cancer Institute Common Toxicity criteria.Univariable and multivariable analysis was performed for progression free (PFS) and overall (OS) survival with age, extent of resection, pathology and cohort as prognostic variables.

Results: 152 patients entered these cohorts. All patients received their vaccinations in an ambulatory setting. There were no serious adverse events except in one relapsed patient with gross tumoral disease prior to vaccination, who developed repetitive vaccine-related peritumoral edema. There is a significantly better PFS and OS for total resection and significantly worse PFS for GBM. Both in the univariable analysis (stratified on cohort) and the multivariable analysis, the effect of age differs significantly between the four cohorts: throughout the cohorts, the beneficial effect for children (HR=0.20; 95%CI=0.08-0.52 in cohort A) progressively weakens and even reverses sign in cohort D (HR=1.42;95%CI=0.77-2.60). Moreover, there is no evidence that the effect of total resection and pathology differs between the cohorts. Considering PFS in adult patients with relapsed GBM, the vast majority of the included patients, the PFS differed significantly between the 4 cohorts (p=0.0097) with cohort D leading to the best PFS. This difference between cohorts was not present for OS

anymore.

Conclusions: Immunotherapy for patients with relapsed HGG is feasible without major adverse events. Long-term (>24 months) survival after relapse is possible in a substantial group of patients. Especially total resection seemed to be an independent, favourable prognostic variable for both PFS and OS after multivariable analysis. The vaccination schedule seems to play a role in building up the immune-mediated control mechanisms in adults with relapsed GBM. Further improvement of the PFS in these patients could be realised by stimulating in vivo the dendritic cells generated ex vivo with Imiquimod.