CTIM-14. RESULTS OF PHASE II STUDY OF NIVOLUMAB FOR PATIENTS WITH MENINGIOMAS REFRACTORY TO SURGERY AND RADIOTHERAPY BASED ON IMMUNE-RELATED RESPONSE CRITERIA WITH MOLECULAR ANALYSES

Abstract A subset of meningiomas, including the majority of grade II/III and a proportion of grade I tumors, are refractory to repetitive resection and radiotherapy, and are frequently fatal. Reports of effective medical therapy are extremely rare. Literature suggests that immune checkpoint systems might have a role in aggressive meningiomas. A single-arm, phase 2 study was conducted to evaluate the efficacy and safety of nivolumab for meningiomas refractory to surgery and radiotherapy. Nivolumab (480 mg) was administered intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) determined by a central independent review committee. To avoid premature discontinuation of potentially effective immunotherapy, response was evaluated based on the iRANO (meningioma) criteria, which is based on the RANO (meningioma) criteria (Neuro Oncol 21:26-36, 2019) with the integration of the immune-related response criteria outlined previously (Lancet Oncol 16:e534-e542, 2015). Archival tumor specimens were obtained from all 29 cases. A total of 29 patients started the study therapy. Response assessment by the central review committee was performed for 28 patients: grade I in 5, grade II in 19, andgrade III in 4 by definition of WHO2016. The best overall response was PR in 1, SD in 13, and uPD/cPD in 14. The ORR was 3.6% and PFS-6 was 23.9%. Nivolumab was well tolerated. There was no case with mutations in the DNA mismatch repair genes. One patient who had multiple grade I meningiomas with biopsy-proven lung metastases showed sustained PR following initial radiological progression. The TMB of the tumor was 8.1/MB. Some specific gene sets were shown to be enriched in the PR case. Although nivolumab monotherapy failed to meet the prespecified primary endpoint, our study demonstrated that a subset of patients could benefit from the therapy and that immune-related response criteria are necessary to evaluate immunotherapy for meningiomas.