In patients with glioblastoma, the “DCVax-L” trial reported a survival benefit with the addition of autologous tumor lysate-loaded denditric cell vaccination to the standard-of-care (SoC) in patients with glioblastoma. The trial presented as a phase 3 externally controlled trial is showing an improvement in overall survival (OS) in patients receiving the vaccine therapy as compared to externally controlled patients, both in the newly diagnosed setting (median OS = 19.3 months versus 16.5 months; HR = 0.80; 98% CI, 0.00–0.94; P = 0.002) and in the recurrent setting (median OS = 13.2 months versus 7.8 months; HR = 0.58; 98% CI, 0.00–0.76; P < 0.001). Interestingly, the original endpoint, progression-free survival (PFS), was not improved by the experimental therapy. While we praise efforts to improve outcomes in a population representing a true unmet need, the trial's design, methods and report raise several issues undermining the ability to derive meaningful conclusion. These limitations are mainly driven by multiple changes occurring years after the trial ended. External controls were used in a trial originally randomizing patients, the primary endpoint was modified (OS instead of PFS), a new study population (recurrent glioblastoma) was added, and unplanned analyses were conducted, among several other changes. Additionally, due to inclusion criteria, the external controls likely selected patients with less favorable outcome as compared with patients enrolled in the trial, potentially biasing the reported survival benefit. In the absence of data sharing, these shortcomings will not be clarified. Dendritic cell vaccination remains a promising approach for GBM. It is therefore disappointing that due to key methodological limitations, the DCVax-L trial ultimately failed to provide sound conclusions about the potential efficacy of such approach for patients with glioblastoma.