Simple SummaryGlioblastoma is the most common of primary brain tumors, accounting for approximately 50% of intracranial malignancies. It is an aggressive neoplasm with a poor prognosis. To date, the standard of care is a treatment involving maximal surgery, radiotherapy concurrent with and followed by maintenance chemotherapy with temozolomide. Despite this multimodal approach and the continuous advances in molecular biology, median survival is 13–14 months and 5-year survival does not exceed 10% of patients. Therefore, the need to develop new treatments that can impact the survival of glioblastoma patients is urgent. After decades of research failures, immunotherapy timidly begins to give the first results in the treatment of this tumor. The publication of the phase III study on the use of the dendritic cell vaccine DCVax-L in glioblastoma has aroused much interest in neuro-oncology. We report the promising results of this trial, which, however, is worthy of a critical debate regarding both the special study design and the authors’ conclusions.AbstractThe lack of significant improvement in the prognosis of patients with GB over the last decades highlights the need for innovative treatments aimed at fighting this malignancy and increasing survival outcomes. The results of the phase III clinical trial of DCVax-L (autologous tumor lysate-loaded dendritic cell vaccination), which has been shown to increase both median survival and long-term survival in newly diagnosed and relapsed glioblastoma, have been enthusiastically received by the scientific community. However, this study deserves some reflections regarding methodological issues related to the primary endpoint change, the long accrual period, and the suboptimal validity of the external control population used as the comparison arm.