NCOG-37. SINGLE CENTER EXPERIENCE OF IDH INHIBITORS IN THE TREATMENT OF RECURRENT HIGH GRADE GLIOMAS

Abstract BACKGROUND The antitumor effect of IDH inhibitors in high grade gliomas (HGG) is not well known, with conflicting views regarding the role of IDH status and the potential for resistance to DNA damage treatments. We present the outcomes of patients with HGG that were treated with IDH inhibitors at our institution. METHODS We performed a retrospective review of patients with IDH mutant gliomas treated with FDA approved IDH inhibitors (ivosidenib and enasidenib) in the past 5 years at our institution. One cycle of IDH inhibitor was defined as treatment for 28 days. RESULTS We identified 10 HGG patients (both oligodendrogliomas and astrocytomas). Median age at diagnosis was 31 years and 7 were male. Seven patients were diagnosed as WHO grade 3. Six patients were WHO grade 3 oligodendrogliomas, three WHO grade 4 astrocytomas, and one patient WHO grade 3 astrocytoma. Only one patient received enasidenib and the rest were treated with ivosidenib. Eight patients were started on IDH inhibitors after 3 recurrences. Median number of cycles was 5. One patient received 23 cycles, and one patient received 11 cycles. All patients underwent resection, 4 received chemotherapy (including temozolomide, bevacizumab, and CCNU), and 4 radiation prior to starting IDH inhibitors. One patient was treated with Tumor Treating Fields. Five patients progressed during the study follow up, and 3 patients died. Four patients are still on treatment. No serious adverse events. Median PFS after starting an IDH inhibitor was 6 months. DISCUSSION IDH inhibitors were well tolerated in IDH mutant HGG patients previously treated with DNA-damaging agents. It may have a role in the treatment of HGG with multiple recurrences with 3 patients showing stable disease for more than 18 months. More studies are needed to clarify the role of IDH inhibitors in patients with IDH mutant HGG.