Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis

Baofeng Guo; Shengnan Zhang; Libo Xu; Jicheng Sun; Wai-Lun Chan; Pengfei Zheng; Jinnan Zhang; Ling Zhang

doi:10.3389/fimmu.2023.966696

Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis

Front Immunol. 2023 Jul 6:14:966696. doi: 10.3389/fimmu.2023.966696. eCollection 2023.

Authors

Baofeng Guo¹, Shengnan Zhang², Libo Xu², Jicheng Sun¹, Wai-Lun Chan³, Pengfei Zheng², Jinnan Zhang^{1

4}, Ling Zhang²

Affiliations

¹ Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
² Department of Pathophysiology, College of Basic Medical Sciences of Jilin University, Changchun, Jilin, China.
³ Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China.
⁴ Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, China.

Abstract

Background: Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.

Method: Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).

Results: We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; Z = -2.00, P = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; Z = -1.99, P = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; P = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; Z = -3.53; P = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; Z = -2.23; P = 0.0256).

Conclusion: Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.

Keywords: glioblastoma; glioma; high-grade; immunotherapy; meta-analysis; radiotherapy; standard of care; temozolomide.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / pathology
Glioma*
Humans
Immunotherapy / adverse effects
Progression-Free Survival
Standard of Care

Grants and funding

The current study was funded by the National Natural Science Foundation of China (Grant No. 82273479 to LZ) and Jilin Province lnnovation and Entrepreneurship Talent Funding Project (Grant No. 2022ZY13 to lZ) and Research Fund of Jilin Provincial Science and Technology Department (Grant No.20210204072YY to BG) and China-Japan Union Hospital and College of Basic Medical Sciences, Jilin University Union Proiect (Grant No. KYXZ2022C05 to LZ). Hong Kong Polytechnic University Startup Fund for RAPs under the Strategic Hiring Scheme (P0035714.W-LC).