Scientific publications

A phase II trial of autologous dendritic cell vaccination and radiochemotherapy following fluorescence-guided surgery in newly diagnosed glioblastoma patients

Inogés S (1,2), Tejada S (3), de Cerio AL (4,5), Pérez-Larraya JG (6), Espinós J (7), Idoate MA (8), Domínguez PD (9), de Eulate RG (9), Aristu J (10), Bendandi M (11,12), Pastor F (13), Alonso M (14), Andreu E (5), Cardoso FP (4,15), Valle RD (16). (1) Cell Therapy Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(2) Immunology and Immunotherapy Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(3) Neurosurgery Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(4) Cell Therapy Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(5) Immunology and Immunotherapy Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(6) Neurology Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(7) Oncology Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(8) Pathology Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(9) Radiology Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(10) Radiation Oncology Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(11) Section on Hematology/Oncology, Department of Internal Medicine, Comprehensive Cancer Center, Wake Forest University Baptist Healthcare Center, Winston-Salem, NC, USA.
(12) Section of Hematology/Oncology, Department of Internal Medicine, W.G Hefner VA Medical Center, Salisbury/Charlotte, NC, USA.
(13) Program of Molecular Therapies, Aptamer Unit, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Avenida Pio XII 55, 31008, Pamplona, Navarra, Spain.
(14) Program in Solid Tumors and Biomarkers, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Avenida Pio XII 55, 31008, Pamplona, Navarra, Spain.
(15) Haematology and Haemotherapy Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
(16) Neurosurgery Department, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain

Magazine: Journal of Transational Medicine

Date: May 12, 2017

Neurosurgery Radiology [SP] Cell Therapy Area [SP] Radiation Oncology Pathological Anatomy [SP] Neurology [SP] Medical Oncology

BACKGROUND:

Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option.

We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival.

METHODS:

We conducted a phase-II clinical trial of autologous DCs vaccination in patients with newly diagnosed patients GBM who were candidates to complete or near complete resection.

Candidates were finally included if residual tumor volume was lower than 1 cc on postoperative radiological examination. Autologous DCs were generated from peripheral blood monocytes and pulsed with autologous whole tumor lysate.

The vaccination calendar started before radiotherapy and was continued during adjuvant chemotherapy. Progression free survival (PFS) and OS were analyzed with the Kaplan-Meier method. Immune response were assessed in blood samples obtained before each vaccines.

RESULTS:

Thirty-two consecutive patients were screened, one of which was a screening failure due to insufficient resection. Median age was 61 years (range 42-70). Karnofsky performance score (KPS) was 90-100 in 29%, 80 in 35.5% and 60-70 in 35.5% of cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in 45.2% of patients.

No severe adverse effects related to immunotherapy were registered. Median PFS was 12.7 months (CI 95% 7-16) and median OS was 23.4 months (95% CI 16-33.1). Increase in post-vaccination tumor specific immune response after vaccines (proliferation or cytokine production) was detected in 11/27 evaluated patients. No correlation between immune response and survival was found.

CONCLUSIONS:

Our results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration.

This phase-II trial was registered as EudraCT: 2009-009879-35 and ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.

CITATION  J Transl Med. 2017 May 12;15(1):104. doi: 10.1186/s12967-017-1202-z

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