Immunotherapy for malignant glioma: current results of the clinical trials

The prognosis of high grade glioma (HGG) is poor in spite of advanced neurosurgery, radio- and chemotherapy. Evidence appears that active specific immunotherapy with mature dendritic cells loaded with tumor lysate (DCm-HGG-L) might induce long term survival. In the cohort comparison trial HGG-IMMUNO-2003 we stepwise explore improvements in the technique for patients with relapsed HGG. Shortening of the interval between the induction vaccines, boosting with only HGG-L and changing the maturation cocktail all improved the efficacy of the vaccine resulting in a remarkable subgroup of long-term survivors. The 3-year survival of adults with relapsed grade IV HGG was 8.3% (n=24) and 14.2% (n=66). A closed culture system for the production of the vaccines is currently explored in a fifth cohort. An update of the clinical data of the patients will be discussed. Next, we integrated in the HGG-2006 trial immunotherapy as part of the multimodal primary treatment of 77 adults with grade IV HGG. The treatment was feasible without major toxicity. The 6-month 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-promotor had significantly better PFS (p=0.0027) and OS (p=0.0082) as compared to patients with an unmethylated status. 'Immunological profiles' were built and compared to clinical outcome, but no statistical significant evidence was found for these profiles to predict clinical outcome. These data serve as basis for the currently running prospective placebo-controlled double-blind phase IIb randomized clinical trial with 6-month PFS as primary endpoint. The design of the trial will be discussed. Overall, we can conclude that immunotherapy for patients with HGG is a treatment option that should be considered when the tumor in the patient can be (sub)totally resected.