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Immune Checkpoint Inhibition for High Grade Meningiomas: A Systematic Review
Joel Kaye1, John Na1, Shravan Atluri2
1Department of Neurological Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Background:
World Health Organization grade II/III meningiomas frequently recur despite maximal safe surgical resection and adjuvant radiation. Notoriously resistant to medical therapy, no well-established guidelines for pharmacologic treatment currently exist. In recent years, a small number of clinical trials have investigated immune checkpoint inhibitors (ICIs) for patients with recurrent grade II/III meningiomas. We reviewed the existing literature to 1) summarize the clinical responses that have been observed and 2) identify tumor genomic characteristics that may predict a better response to ICI therapy.
Methods:
PubMed was searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to include studies reporting clinical data for recurrent grade II or grade III meningiomas treated with ICIs. Clinical features, available tumor genomics, and outcomes were analyzed.
Results:
Four studies were included comprising 59 patients; 74.6% had World Health Organization grade II meningiomas and 25.4% had grade III meningiomas. Thirt-two patients (54%) received nivolumab, 26 (44%) received pembrolizumab, and 1 (2%) received an ICI not named. While tumor genomic data was not consistently reported across studies, favorable response was most associated with mismatch repair deficiency and high tumor mutational burden. Common adverse effects included liver/pancreas enzyme elevations (11.5%), fatigue (11.5%), and leukopenia/infection (9%).
Conclusions:
Checkpoint inhibitors represent a promising investigational therapy for patients with recurrent grade II/III meningiomas. These drugs may be more efficacious for tumors with mismatch repair deficiency or high tumor mutational burden. Future investigations would benefit from research consortia with prospective enrollments of patients, descriptive characterization of tumor genomics, and standardized assessment of radiographic response.
Insights
Immune checkpoint inhibitors show promise for recurrent meningiomas. Tumors with mismatch repair deficiency or high tumor mutational burden may respond better to these therapies.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Genomics
Background:
- World Health Organization grade II/III meningiomas often recur after standard treatment.
- Effective medical therapies for recurrent meningiomas are lacking.
- Immune checkpoint inhibitors (ICIs) are being investigated for these challenging cases.
Approach:
- Systematic literature review following PRISMA guidelines.
- Analysis of clinical data, tumor genomics, and outcomes from studies on recurrent meningiomas treated with ICIs.
- Inclusion of four studies with 59 patients.
Key Points:
- Nivolumab and pembrolizumab were the most common ICIs used.
- Favorable responses were associated with mismatch repair deficiency and high tumor mutational burden.
- Common adverse effects included elevated liver/pancreas enzymes, fatigue, and leukopenia/infection.
Conclusions:
- ICIs offer a promising therapeutic avenue for recurrent grade II/III meningiomas.
- Tumor genomics, specifically mismatch repair deficiency and high tumor mutational burden, may predict ICI efficacy.
- Future research should focus on prospective trials with standardized genomic and response assessments.
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