A phase II trial of autologous dendritic cell vaccination and radiochemotherapy following fuorescence-guided surgery in newly diagnosed glioblastoma patients
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 t...
| Autores: | , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | español |
| OAI Identifier: | oai:dadun.unav.edu:10171/68486 |
| Acesso em linha: | https://hdl.handle.net/10171/68486 |
| Access Level: | acceso abierto |
| Palavra-chave: | Materias Investigacion::Ciencias de la Salud::Radiología Glioblastoma Immunotherapy Dendritic cell Overall survival |
| Resumo: | 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 hypoth‐ esized 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 fnally 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 insufcient 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 efects 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 specifc immune response after vaccines (proliferation or cytokine production) was detected in 11/27 evaluated patients. No correla‐ tion 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 beneft of this therapeutic approach. |
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