1. Patients receiving autologous tumour lysate-loaded dendritic cell vaccine (DCVax-L) had a 20% relative reduction in death risk.
2. DCVax-L appears safe, with only 5 of 2,151 (0.2%) doses resulting in serious adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The prognosis for glioblastoma is poor, as it remains the primary brain cancer with the highest mortality. This study investigated whether the addition of an autologous tumour lysate-loaded dendritic cell vaccine (DCVax-L) to the traditional standard of treatment (surgery, radiotherapy, and chemotherapy) for glioblastoma prolonged survival. This study’s primary outcome included overall survival (OS), and the secondary outcome included safety in patients receiving DCVax-L in conjunction with standard treatment as compared to external control patients. The median OS was longer at 19.3 months in the patient group receiving DCVax-L as compared to the external control group at 16.5 months, and the OS remained significantly greater in the DCVax-L group in 5 years. Only a few adverse events (AEs) occurred with the administration of DCVax-L. Of the patients who received DCVax-L, none were reported to have auto-immune reactions or cytokine storms. Limitations to this study include a fairly small sample size and limitations to the usage of progression-free survival metrics due to the nature of the disease. Additionally, the placebo group was gradually lost to crossover, necessitating the use of an external control group that did not have patient-level data available. As a result, conclusions should be interpreted cautiously. Overall, the results from this study suggest that the use of DCVax-L is promising in extending survival for patients with newly diagnosed glioblastoma who are also receiving standard treatment for their disease.
In-Depth [non-randomized controlled trial]: This phase 3 nonrandomized controlled trial enrolled 331 patients from 94 sites in multiple countries and randomly allocated them in a 2:1 manner to DCVax-L (n=232) or placebo (n=99). As a result of the requirement for invasive leukapheresis in all patients, including those randomized to placebo, the trial opted to utilize a cross-over design, ensuring that all patients had access to an autologous vaccine. Therefore, external controls were used to compare and evaluate OS. The OS comparator group of external control patients were 1,366 patients with glioblastoma from other randomized controlled trials (RCTs) who were receiving standard treatment. In patients receiving the DCVax-L, the median OS was 19.3 months from randomization (95% confidence interval (CI), 17.5 – 21.3 months) when compared with 16.5 months (95% CI, 16.0 – 17.5) in the external control group (log-rank hazard ratio (lrHR), 0.80; 95% CI, 0.00-0.94). This reduction in risk of death remained significantly greater in the DCVax-L group over time to 60 months, even after adjustment for imbalances between groups. Regarding safety, there were 2,151 doses of DCVax-L provided and only 5 (0.2%) serious AEs potentially related to the vaccine. AEs included intracranial edema, nausea, and lymph-node infection. There were no reported auto-immune adverse reactions or cytokine storms among those who had DCVax-L.
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