INNV-14. Real world use of Ivosidenib for patients with recurrent IDH mutant gliomas

Abstract BACKGROUND IDH mutant gliomas are the most common primary malignant brain tumors in adults under the age of 50 with a paucity of effective treatment options in the recurrent setting. Mutations in IDH1/ 2 occur upwards of 80% of patients with LGG and drive specific epigenetic programs to dysregulate and impair differentiation leading to tumorigenesis. Ivosidenib (AG-120), a second-generation IDH inhibitor, is an FDA-approved treatment for IDH-mutated AML and has demonstrated safety and clinical activity in patients with progressive IDHm gliomas. METHODS We retrospectively analyzed patients with IDHm gliomas treated with at least one cycle of ivosidenib. Data collected included demographics, tumor histology, tumor location, grade, 1p/19q co-deletion, MGMT, CDKN2A, TERT, EGFR, P53, PTEN mutational status, prior treatment history, duration of treatment, toxicities, radiographic response, and survival. Descriptive statistics and Kaplan-Meier method were used to summarize patient’s characteristics and survival, respectively. RESULTS Between 4/2010-12/2023, 33 patients had received ivosidenib. 7 patients received ivosidenib plus bevacizumab, 3 patients received ivosidenib plus radiation, and 1 patient received ivosidenib plus nivolumab. The median age was 52 (range 31-81). 21 (63%) were male. The median lines of prior medical therapy and radiation/surgery were 3.03(range 0-6) and 1.5(range 0-4), respectively. 27(81%) were grade 2, 5(15%) were grade 3, and 1(3%) were grade 4. 19(57%) had 1p/19q co-deletion. As of 12/31/2024, 39%(13) patients were alive. The mPFS was 7.52 months (1-26) and mOS 12.7 months (3-25). 11(33%) patients experienced PR, 20(60%) experienced SD and 2(6%) demonstrated PD at 12-week assessment. Nine patients experienced AEs: grade 1 fatigue (3), grade 1 diarrhea (1), grade 2 fever (1), grade 2 weakness (1), and grade 3 confusion (1). One grade 4 lobar hemorrhage thought to be related to concurrent bevacizumab use. CONCLUSION Treatment with Ivosidenib was safe, and in a subset of patients, there was disease stabilization in heavily pre-treated recurrent IDHm gliomas.