CTIM-31. PRELIMINARY RESULTS OF A PHASE II STUDY OF STEREOTACTIC RADIOSURGERY IN CONJUNCTION WITH THE PD-1 INHIBITOR PEMBROLIZUMAB FOR THE TREATMENT OF RECURRENT HIGH-GRADE MENINGIOMA

Abstract Recurrence of higher-grade meningioma after initial resection and radiotherapy is frequent and associated with high rates of morbidity and mortality. Salvage therapies have limited efficacy and average survival after recurrence is approximately 5-10 years. We report here preliminary data from a phase 2 study combining immunotherapy with checkpoint inhibition with stereotactic radiosurgery for treatment of recurrent high-grade meningioma (NCT04659811). Adult patients with either grade 2 or 3 meningioma who have recurred despite treatment with surgery and radiation and who meet eligibility criteria received stereotactic radiosurgery, in 1 to 5 fractions, in conjunction with pembrolizumab 200mg on the first day of radiation and then every 3 weeks until progression, unacceptable toxicity or for 2 years. Primary objective is PFS12, and secondary objectives include safety of the combined treatment in recurrent meningioma, mOS, mPFS, and neurocognitive function and QOL metrics. To date we have enrolled 18 of planned 37 patients, 33% female, 39% grade 2 and 61% grade 3. Safety lead in was completed without any dose limiting toxicity. There have been 4 SAEs, only one of which was related to study treatment (cerebral edema). 29% of patients had at least one AE, the most common were GI disorders (23%), skin disorders (23%) and headache (17%). Preliminary data from 12 patients shows PFS12 to be 50%, which suggests that the combination of stereotactic radiosurgery may be more beneficial than treatment of Pembrolizumab alone (mPFS 7.6 months). One patient was found to have a homozygous focal deletion of the MLH1 gene and had a dramatic reduction in size of her meningioma with a durable response for over one year. These preliminary data suggest that the combination of stereotactic radiosurgery and pembrolizumab is safe, well tolerated and may be beneficial to patients with recurrent higher-grade meningioma.