INNV-11. USE OF IVOSIDENIB IN THE TREATMENT OF LOW GRADE GLIOMAS

Abstract

Abstract IDH 1 and IDH 2 are crucial metabolic enzymes which covert isocitrate to alpha-ketoglutarate. During this process, NADP is reduced to NADPH. Mutant IDH produces an oncometabolite, D-2 hydroxyglutarate (2-HG). Elevated 2-HG levels interfere with epigenetic regulation and cellular metabolism leading to oncogenesis and have been postulated to play a role in multiple malignancies. Mutations in IDH1 and IDH2 have been found in AML, cholangiocarcinoma, myeloproliferative, myelodysplastic syndromes, and low-grade gliomas. IDH inhibitors, although not FDA approved for treatment of glioma, have shown promise as a treatment for low-grade gliomas with IDH mutation in clinical trials. Ivosidenib is an orally available inhibitor of IDH1. We examined patients with oligodendroglioma treated off-label with ivosidenib. RANO criteria for low grade glioma was used to determine radiographic response following ivosidenib initiation. Patient ages 28 , 37 , and 37 females with oligodendroglioma, IDH1 mutated, 1p/19q co-deleted, WHO grade 2 were treated with ivosidenib. Treatment was initiated between August 2022 and March 2023. Two patients had two prior recurrences each while the third patient was treated in the neoadjuvant setting following subtotal resection. Two had stable disease as best response at follow-up of 7 and 17 months while the third is awaiting interval follow up. Duration of ivosidenib therapy was 9, 19, and 3 months respectively and is ongoing in all patients. Only grade 1 leukopenia was observed in one patient which resolved without intervention. No seizures since surgery were observed in two patients, while yearly focal seizures occurred in the third patient. Median progression free survival was not able to be determined, however preliminary data reveals stable disease as best response in all three patients without side effects or increased seizure frequency. IDH inhibitors continue to be an area of interest and ongoing research in the treatment of low-grade glioma.