Checkpoint inhibitor failure in hypermutated and mismatch repair-mutated recurrent high-grade gliomas.

ABSTRACT

BACKGROUND: Recurrent high-grade gliomas in adults remain a deadly cancer with median survival of less than 1 year. In the absence of effective agents, immunotherapy with checkpoint inhibitors has been adopted as a potentially beneficial next step for recurrences with hypermutated or mismatch repair-mutated phenotypes. The rationale for their use, however, is based on case reports and studies with other types of cancer. METHODS: We reviewed 4 cases of hypermutated or mismatch repair-mutated recurrent high-grade gliomas treated with checkpoint inhibitors. RESULTS: All cases had recurrent high-grade glioma that harbored either a hypermutated phenotype and/or a mismatch repair mutation. Treatment with checkpoint inhibitor therapy resulted in no significant response. CONCLUSIONS: In our experience, hypermutated or mismatch repair-mutated high-grade gliomas in adults do not respond to checkpoint inhibitors alone. This lack of efficacy is in agreement with underwhelming results of clinical trials examining checkpoint inhibitors in high-grade gliomas. The case reports of responders have been in pediatric patients with glioma and are likely a different subtype altogether.