No abstract

Purpose:To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. Experimental Design: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. Results: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. Conclusion: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.In spite of multimodal therapy, including maximal safe neurosurgical resection followed by radiochemotherapy and maintenance chemotherapy, malignant or high-grade gliomas (HGG) continue to have a dismal prognosis (1). Prognosis after relapse is even worse (2, 3), with a median progression-free survival (PFS) of 2 months, and virtually all patients being dead 18 months after the relapse. Even in pediatric patients with relapsed HGG, the prognosis is poor (4).The rationale, the preclinical, and the early clinical evidence to develop dendritic cell (DC)-based immunotherapy for HGG has been reviewed by our research group (5, 6) and by others (7 -14). Vaccination is done with autologous mature monocyte-derived ex vivo generated DC loaded with autologous tumor lysate. The characteristics and in vitro function of the vaccine have been analyzed (15, 16). We described some early clinical experience on feasibility and toxicity that we obtained in a small group of patients (17,18).For the implementation of immunotherapy in clinical practice for patients with relapsed HGG, an observational prospective cohort comparison trial, HGG-IMMUNO, was designed, in which adjuvant autologous DC vaccination is done in patients with relapsed HGG after maximal new resection of the relapsed tumor. Except for the time window in cohort A, which was the

Patients with relapsed malignant glioma have a poor prognosis. We developed a strategy of vaccination using autologous mature dendritic cells loaded with autologous tumour homogenate. In total, 12 patients with a median age of 36 years (range: 11 -78) were treated. All had relapsing malignant glioma. After surgery, vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5 (range: 2 -7) vaccines was given. There were no serious adverse events except in one patient with gross residual tumour prior to vaccination, who repetitively developed vaccine-related peritumoral oedema. Minor toxicities were recorded in four out of 12 patients. In six patients with postoperative residual tumour, vaccination induced one stable disease during 8 weeks, and one partial response. Two of six patients with complete resection are in CCR for 3 years. Tumour vaccination for patients with relapsed malignant glioma is feasible and likely beneficial for patients with minimal residual tumour burden.

No abstract