Safety and Efficacy of Chimeric Antigen Receptor T-cell Therapy for Recurrent Glioblastoma: An Augmented Meta-analysis of Phase 1 Clinical Trials
Rédigé par Ahmed Y. Azzam , Mahmoud M. Morsy , Mohammed A. Azab , Osman Elamin , Adam Elswedy , Omar S. Ahmed , Mahmoud Nassar , Ahmed Saad Al Zomia , Adham A. Mohamed , Oday Atallah , Ahmed Alamoud , Hammam A. Alotaibi , Hana J. Abukhadijah et Abdulqadir J Nashwan
Publié 24 octobre 2024
Serveur de preprints medRxiv
Introduction
Glioblastoma is a devastating brain tumor with poor prognosis despite current treatment modalities. Chimeric antigen receptor T-cell (CAR T-cell) therapy has shown promise in other cancers but has yielded mixed results in glioblastoma. This augmented meta-analysis aims to address the limitations of previous studies and evaluate the safety and efficacy of CAR T-cell therapy for recurrent glioblastoma.
Methods
We followed PRISMA guidelines, including specific inclusion and exclusion criteria, for our literature review. Eight studies with 108 patients were included. We used standard and augmented meta-analyses to assess outcomes, complications, and publication bias.
Results
It was found that the mean overall survival for glioblastoma patients who underwent CAR T-cell therapy was 6.49 months, demonstrating no significant deviation from the median survival observed in those following the standard protocol. CAR T-cell therapy did not lead to a statistically significant improvement in achieving complete responses, with only 80% of patients exhibiting this outcome. Conversely, 44% of patients experienced stable disease, while 58% faced disease progression after CAR T-cell therapy. Adverse events were notable, with CAR T cell therapy-related encephalopathy affecting 37% of treated patients, while cytokine release syndrome was a rare event, observed in only 3% of cases.
Conclusions
To our knowledge, this is the first study that utilizes this novel statistical technique to predict the outcomes of CAR T-cell therapy for recurrent glioblastoma. The results of this study are predictive rather than confirmatory. CAR T-cell therapy for glioblastoma was not predicted to significantly improve survival or achieve substantial complete responses. Stable disease rates are modest, while disease progression is notable. Adverse events, especially CAR T-cell therapy-related encephalopathy, raise safety concerns. Further trials and refinements are needed to enhance CAR T-cell therapy’s effectiveness and safety in glioblastoma treatment, Manuscript Click here to view linked References potentially through optimizing administration routes and target antigens or combining it with other therapies. This challenging disease necessitates continued research to improve patient outcomes.