Journal Article

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

Idoate, Miguel Angel, Cardoso, Felipe Prósper, Gállego Pérez-Larraya, Jaime, Aristu, Javier, Bendandi, Maurizio, Tejada, Sonia, Domínguez, Pablo Daniel, Pastor, Fernando, Espinós, Jaime, Valle, Ricardo Díez, Inogés, Susana, Alonso, Marta, de Cerio, Ascensión López-Díaz, Andreu, Enrique, de Eulate, Reyes García

2017

Overview

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 (O 6 -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

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Biomedical and Life Sciences / Biomedicine / Brain cancer / Cancer / Cancer therapies / Care and treatment / Chemoradiotherapy / Chemotherapy / Clinical trials / Dendritic cell / Dendritic cells / Diagnosis / DNA methyltransferase / Fluorescence microscopy / Glioblastoma / Glioblastoma multiforme / Health aspects / Hepatitis / Immunobiology and immunotherapy / Immunotherapy / Medical prognosis / Medicine/Public Health / Monocytes / Multivariate analysis / Neurosurgery / NMR / Nuclear magnetic resonance / O6-methylguanine-DNA methyltransferase / Overall survival / Patients / Peripheral blood / Prognosis / Radiation therapy / Side effects / Surgery / Survival / Temozolomide / Tumors / Vaccination / Volumetric analysis