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Meningiomas are the most common primary tumor of the central nervous system, with ~28,000 new diagnoses annually in the United States1. Currently, there are no approved systemic therapies for meningiomas that recur following local treatment: chemotherapy and hormonal agents have demonstrated minimal benefit in numerous clinical trials2–4.  Meningioma comprises a heterogeneous group of neoplasms driven by mutations in a wide array of tumor suppressor genes and oncogenes5–17. Characterization of these mutations has revealed opportunities for rational therapy18–20. For example, a durable therapeutic response has been reported for a metastatic AKT1(E17K)-mutant meningioma treated with a pan-AKT inhibitor.21  Studies also suggest the potential for treating meningioma with immune checkpoint modulators22–24: programmed death receptor 1 ligand (PD-L1) is expressed in a subset of meningiomas and the tumor microenvironment is immunosuppressive22–28. Higher-grade meningiomas also harbor mutations predicted to generate neoantigens, which may foster susceptibility to immunotherapies29.  Based on these data, we initiated a phase II study of nivolumab, a humanized IgG4 PD-1 blocking monoclonal antibody, in patients with higher-grade meningiomas that recurred following surgery and radiotherapy ({"type":"clinical-trial","attrs":{"text":"NCT02648997","term_id":"NCT02648997"}}NCT02648997). We report here a patient with an atypical meningioma that was not controlled by repeated surgery and radiation but which was highly response to nivolumab.

jco precision oncology

Mismatch Repair Deficiency in High-Grade Meningioma: A Rare but Recurrent Event Associated With Dramatic Immune Activation and Clinical Response to PD-1 Blockade