Meta-Analysis of Treatment-Emergent Seizures in Glioma Vaccine Trials
Abstract number :
2.267
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2025
Submission ID :
128
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Louise Mc Carthy, MB BCh BAO – Mass General Brigham
Brian Andersen, MD – Mass General Brigham
David Reardon, MD – Dana-Farber Cancer Institute
Steven Tobochnik, MD – Dana-Farber Cancer Institute
Rationale: Epilepsy is commonly associated with gliomas, and recent evidence has established glioma-neuron hyperexcitability as a mechanism promoting tumor growth. However, immune-mediated effects on hyperexcitability in the tumor microenvironment are uncertain. Epilepsy maintains a proinflammatory state, whereas gliomas manipulate the microenvironment to evade adaptive immunity and promote tumor progression. Glioma vaccines have emerged as a promising form of immunotherapy and may serve as a model to study these interactions. This meta-analysis aimed to evaluate the incidence of seizures after glioma vaccine therapy as a clinical marker of peritumoral hyperexcitability.
Methods: Studies were identified by MESH queries of the MEDLINE database filtered for clinical trials, review of references, and query of clinicaltrials.gov. Inclusion criteria were prospective trials of cancer vaccines in patients with histologically confirmed diffuse glioma. Studies were excluded if seizure incidence was not reported or if patient-level data for all adverse events (AEs) regardless of treatment attribution was unavailable. Serious AEs were defined as grade 3 or higher by the Common Terminology Criteria for Adverse Events (CTCAE) when available. Seizure incidence was calculated by pooled proportions with random effects using a generalized linear mixed model. Binary outcome meta-analysis of controlled trials was performed using the Mantel-Haenszel method, with random effects and heterogeneity estimated by the Restricted Maximum Likelihood method. All analyses were performed using R 4.2.2.
Results: A total of 114 studies were identified. After excluding trials with missing seizure or AE data (n=57), duplicate analyses (n=11), non-vaccine trials (n=4), non-glioma pathologies (n=3), and incomplete reports (n=3), the final analysis included 33 studies of 1306 vaccine-treated patients. AE reporting was performed using CTCAE v5.0 (n=1), v4.0 (n=16), v3.0 (n=8), v2.0 (n=2), or not specified (n=5). Treatment-emergent seizures of any grade occurred in 18.2% of patients (95% CI: 14.9-21.9%). Serious seizure AEs occurred in 3.5% (95% CI: 1.9-6.4%). In controlled trials, seizure rates of any grade were similar between vaccine and control groups (RR 0.90, 95% CI: 0.68-1.19, I2 = 0%), as well as for serious seizure AEs (RR 0.88, 95% CI: 0.46-1.68, I2 = 0%). There were no differences observed in seizure risk between dendritic cell, tumor cell, and peptide vaccines (p=0.61).
Conclusions: Pre- and post-treatment seizure data was not available for the majority of glioma vaccine trials, likely due to lack of attribution to vaccine treatment. When reported, seizures occurred in nearly 1 in 5 patients over the course of vaccine treatment and trial monitoring. There was no evidence for increased risk of seizures with glioma vaccines overall or for any vaccine subtype. Integrating standardized detailed seizure assessments into future glioma trials may improve response assessments.
Funding: N/A
Clinical Epilepsy