Vaccine immunotherapy for glioblastoma: How can previous attempts guide us?

[BACKGROUND] Yearly, glioblastoma (GBM) is the cause of death of thousands of people in the US. It is paradoxically one of the most lethal and frequent central nervous system malignancies, occupying a unique position in cancer research. Among various attempted management strategies, vaccine immunotherapy has undergone multiple investigations, with heterogenous results.

[METHODS] A systematic review was undertaken on two databases to identify studies evaluating vaccine immunotherapy survival response in glioblastoma or high-grade malignant glioma. A subgroup meta-analysis of overall survival hazard ratios, a meta-regression and multi-trial Kaplan-Meier curves were delineated via reconstructed survival data.

[RESULTS] 537 studies were found, and 36 were eligible for inclusion. Out of these, 12 had comparable arms for meta-analysis. There was a 49 % [26 %; 64 %] death hazard reduction in the pooled analysis. Only the dendritic cell-based vaccines showed benefit when groups were tested separately. The multi-trial curve suggested a disparity among different approaches. For newly diagnosed GBM, the median overall survival was 18.9 months, ranging from 15.36 to 31.46 months. For recurrent GBM or mixed trials, the median overall survival was 13.9 months, ranging from 9.71 to 15.53 months.

[CONCLUSION] Vaccine immunotherapy for GBM appears to depend on dendritic cells to achieve significant improvements in survival. The incorporation of innate immunity modulators such as GM-CSF and Poly-ICLC, along with stratification by MGMT-methylation, are promising. Although an expressive HR reduction was achieved, there are still primary scientific validity concerns, the residual hazard leads to a reserved prognosis and should be addressed by multimodal treatment approaches.