A Dendritic-Cell Vaccine Made with Cancer Cells for GBM Brain Tumours

For the aggressive brain tumour GBM (glioblastoma), adding a tumour lysate-loaded dendritic-cell vaccine—stimulated with molecules from the patient’s own tumour tissue—called DCVax-L to standard care improved survival in newly diagnosed and recurrent glioblastoma. Results of this phase III trial were published on 17 November 2022 in JAMA Oncology.

Dendritic cells are known as “professor cells” that educate the immune system. They are a type of antigen-presenting cell, stimulating B and T lymphocytes by presenting antigens. They link innate immunity with the  adaptive immune system.

Study Details

The study included 232 patients with newly diagnosed, operated glioblastoma and 64 at first recurrence, treated with DCVax-L plus standard care at centres in four countries between August 2007 and November 2015.

Standard treatment was temozolomide for newly diagnosed patients and lomustine, bevacizumab or best supportive care for recurrent glioblastoma.

DCVax-L was given on days 0, 10 and 20 and at months 2, 4, 8, 12, 18, 24 and 30. Each dose was an intradermal injection of 2.5 million dendritic cells.

Results were compared with external controls from 5 randomised trials involving 1,366 newly diagnosed GBM patients and 10 randomised trials involving 640 with recurrent GBM.

Key Findings

• Median overall survival with DCVax-L in newly diagnosed glioblastoma among 232 patients was 19.3 months (95% confidence interval [CI] = 17.5–21.3 months), versus 16.5 months in controls (95% CI = 16.0–17.5). Vaccination reduced mortality risk by 20% in this group [HR] = 0.80, 98% CI = 0.00–0.94, P = 0.002).
• In tumours with positive MGMT methylation, median overall survival with DCVax-L in newly diagnosed glioblastoma among 90 patients was 30.2 months (95% CI = 23.7–33.9 months), versus 21.3 months among 199 controls (95% CI = 18.3–25.1 months) (HR = 0.74, 95% CI = 0.55–1.00, P = 0.03). A 26% reduction in mortality risk.
• With DCVax-L, in recurrent glioblastoma among 64 patients, median overall survival was 13.2 months (95% CI = 9.7–16.8 months), versus 7.8 months in external controls (95% CI = 7.2–8.2 months) (HR = 0.58, 98% CI = 0.00–0.76, P < 0.001). A 42% reduction in mortality risk.

About 300 patients received a total of 2,151 DCVax-L doses.

Five serious adverse effects were considered at least possibly vaccine-related: three cerebral oedema cases (two grade 3 and one grade 2), one nausea case (grade 3) and one lymph-node infection (grade 3). No autoimmune reactions or cytokine storm were observed.

In conclusion, adding DCVax-L to standard treatment significantly extended survival, clinically and statistically, compared with standard care alone in both newly diagnosed and recurrent glioblastoma. The study also emphasises considering immunotherapy approaches such as dendritic cancer vaccines at earlier stages. 

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