Retrospective study of ivosidenib for patients with recurrent IDH mutant gliomas.

2040 Background: IDH mutant gliomas are the most common primary malignant brain tumors in adults under the age of 50 and accounts for approximately 12% of all glioma diagnoses each year. While lower grade gliomas (LGG) encompassing WHO grades II and III are less aggressive than their higher-grade counterparts, treatment is not curative, and most patients develop tumor recurrence in which there are a paucity of effective treatment options. 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. As such, pharmacologic blockage of IDH mutant enzymes is being actively investigated as potential treatment option. Ivosidenib (AG-120), a second-generation IDH inhibitor, is an FDA approved medication for treatment of IDH-mutated acute myeloid leukemia and has demonstrated safety and clinical activity in patients with progressive IDH mutant gliomas. We explored the efficacy of Ivosidenib in IDH mutant gliomas. Methods: We retrospectively analyzed patients with IDHm gliomas treated with ivosidenib in our institution. We included patients with an IDH1 mutation who received at least one cycle of ivosidenib. Data collected included patient 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, PFS, and OS. Descriptive statistics were used to summarize patients' characteristics. The distribution of mPFS was estimated by the Kaplan-Meier method. Results: Between April 2010 and December 2023, we identified 33 patients that received ivosidenib. 7 patients received ivosidenib in combination with bevacizumab, 3 patients received ivosidenib in combination with radiation, and 1 patient received ivosidenib and nivolumab. The median age was 52 (range 31-81). 21 (63%) were male. The median lines of medical therapy and radiation/surgery prior to starting ivosidenib 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 12/31/2023, 48%(16) patients were alive. The median PFS was 7.52 months (1-26) and median OS 12.7 months (3-25). 11(33%) patients experienced partial response (PR), 20(60%) experienced stable disease (SD) and 2(6%) demonstrated progressive disease (PD) at 12-week assessment. Nine patients experienced adverse events: grade 1 fatigue (3), grade 1 diarrhea (1), grade 2 fever (1), grade 2 weakness (1), and grade 3 confusion (1). One patient experienced grade 4 lobar hemorrhage thought to be related to concurrent bevacizumab use. Conclusions: Treatment with Ivosidenib therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent IDH mutant gliomas.