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Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial

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Abstract

Purpose

Dendritic cell (DC)-based tumor vaccination has rendered promising results in relapsed high-grade glioma patients. In the HGG-2006 trial (EudraCT 2006-002881-20), feasibility, toxicity, and clinical efficacy of the full integration of DC-based tumor vaccination into standard postoperative radiochemotherapy are studied in 77 patients with newly diagnosed glioblastoma.

Patients and methods

Autologous DC are generated after leukapheresis, which is performed before the start of radiochemotherapy. Four weekly induction vaccines are administered after the 6-week course of concomitant radiochemotherapy. During maintenance chemotherapy, 4 boost vaccines are given. Feasibility and progression-free survival (PFS) at 6 months (6mo-PFS) are the primary end points. Overall survival (OS) and immune profiling, rather than monitoring, as assessed in patients’ blood samples, are the secondary end points. Analysis has been done on intent-to-treat basis.

Results

The treatment was feasible without major toxicity. The 6mo-PFS was 70.1 % from inclusion. Median OS was 18.3 months. Outcome improved significantly with lower EORTC RPA classification. Median OS was 39.7, 18.3, and 10.7 months for RPA classes III, IV, and V, respectively. Patients with a methylated MGMT promoter had significantly better PFS (p = 0.0027) and OS (p = 0.0082) as compared to patients with an unmethylated status. Exploratory “immunological profiles” were built to compare to clinical outcome, but no statistical significant evidence was found for these profiles to predict clinical outcome.

Conclusion

Full integration of autologous DC-based tumor vaccination into standard postoperative radiochemotherapy for newly diagnosed glioblastoma seems safe and possibly beneficial. These results were used to power the currently running phase IIb randomized clinical trial.

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Acknowledgments

We thank our laboratory collaborators for their excellent technical assistance, the department of hematology for the care provided at time of the leukapheresis, and the clinic for radiotherapy for irradiating the tumor lysate preparations. HSA has been provided by the Belgian Red Cross and Baxter. This project is supported by the Olivia Hendrickx Research Fund (http://www.olivia.be), the Herman Memorial Research Fund (http://www.hmrf.be), and the James E. Kearney Memorial Foundation (http://www.jekfoundation.org). Support was also obtained from CAF Belgium, Baxter, and gifts from private families and service clubs. Additionally, grants were obtained from “Stichting tegen Kanker”, IWT (TBM projects), the Stem Cell Institute Leuven, the Emmanuel van der Schueren Fund, the International Union against Cancer, the Klinisch Onderzoeksfonds UZ Leuven, and the Fund for Scientific Research—Flanders (FWO-V). SDV is supported by the “Klinisch onderzoeksfonds” from the University Hospital Leuven. SWVG is Senior Clinical Investigator of the Fund for Scientific Research—Flanders (Belgium) (F.W.O.-Vlaanderen).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Catholic University of Leuven, Leuven, Belgium

    Hilko Ardon, Jan Goffin, Frank Van Calenbergh & Steven De Vleeschouwer

  2. Department of Experimental Medicine, Catholic University of Leuven, Leuven, Belgium

    Stefaan W. Van Gool, Tina Verschuere & Wim Maes

  3. Department of Biostatistics and Statistical Bioinformatics, Catholic University of Leuven, Leuven, Belgium

    Steffen Fieuws

  4. Department of Pathology, Catholic University of Leuven, Leuven, Belgium

    Raf Sciot

  5. Department of Imaging, Catholic University of Leuven, Leuven, Belgium

    Guido Wilms & Philippe Demaerel

  6. Department of Radiotherapy, Catholic University of Leuven, Leuven, Belgium

    Johan Menten

  7. Department of Oncology, Catholic University of Leuven, Leuven, Belgium

    Paul Clement

  8. Department of Child and Women, Catholic University of Leuven, Leuven, Belgium

    Stefaan W. Van Gool

  9. Department of Human Genetics, Catholic University of Leuven, Leuven, Belgium

    Maria Debiec-Rychter

  10. Department of Neurosurgery, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium

    Steven De Vleeschouwer & Steven De Vleeschouwer

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  1. Hilko Ardon
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  2. Stefaan W. Van Gool
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Correspondence to Steven De Vleeschouwer.

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Ardon, H., Van Gool, S.W., Verschuere, T. et al. Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother 61, 2033–2044 (2012). https://doi.org/10.1007/s00262-012-1261-1

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  • DOI: https://doi.org/10.1007/s00262-012-1261-1

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