BIOM-63. MOLECULAR FEATURES OF AGGRESSIVE MMR DEFICIENCY BRAIN TUMORS AND RESPONSE TO IMMUNOTHERAPY

Abstract BACKGROUND Primary Brain tumors (PBT) can be divided in two macroscopic categories: glioma and non-glioma. They may harbor different molecular alterations, apart from the more classical in MGMT and IDH. MSI/dMMR status has been evaluated in solid tumors as a predictive biomarker of response to immunotherapy however it is unclear in PBTs. METHODS We evaluated patients with glioma or non-glioma defined by the 2021 WHO classification who were treated at MD Anderson Cancer Center from 2018 to 2023. All the information were extrapolated from MDA database. MMR was defined as deficit in mismatch repair genes: MSH6, MLH1, MSH2, PMS2. All patients’ molecular status was analyzed with either immunochemistry or next generation sequencing. We then identified all patients with dMMR condition who were exposed to immune checkpoint inhibitor (ICI) therapy. Overall survival (OS) and progression free survival (PFS) outcomes were calculated as the time from ICI start until the date of recurrence. RESULTS We identified 21 patients with PBT and ICI therapy. 16 with gliomas: respectively 13 grade 4 glioblastoma, 2 grade 3 astrocytoma, 1 grade 4 astrocytoma. and 5 with non-gliomas: 1 pineal tumor, 3 grade 2 meningioma, 1 high grade ACTH-secreting pituitary carcinoma. For gliomas, the PFS was 28.6 months and the OS was 32.5 months. The most frequent MMR mutation was MSH2, co-mutations were NOTCH, BRCA and POLE. For non-gliomas, the PFS was 74.6 months and OS was 97.36 months. The most representative MMR mutation still was MSH2 and co-mutation found was NF2 CONCLUSIONS Treatment with ICI in certain population of PBTs may be associated with longer survival than historical controls. Further investigation is needed to determine whether dMMR can be a predictor due to its important clinical implication.