Single center experience of IDH inhibitors in recurrent high-grade gliomas

Abstract

Purpose: The role of IDH inhibitors in recurrent high-grade gliomas (HGG) is not well described. We present the outcomes of patients with HGG that were treated with these agents at our institution.

Methods: We reviewed patients with recurrent IDH-mutant HGG treated with FDA approved IDH inhibitors (ivosidenib, enasidenib, and vorasidenib) from December 2019 to December 2024 at the University of Texas MD Anderson Cancer Center.

Results: 23 patients were identified of which 65.2% were male. Tumors included astrocytoma (n = 14, 60.9%) and WHO grade 3 oligodendroglioma (n = 9, 39.1%), with four patients having a WHO grade 4 astrocytoma and 10 a WHO grade 3 astrocytoma. Twenty patients had enhancing disease at the time an IDH inhibitor was recommended. One patient was treated with enasidenib, 17 with ivosidenib, and 5 with vorasidenib. Of those initially treated with ivosidenib, 9 were switched to vorasidenib. Two patients discontinued the drugs due to side effects, that included elevated liver enzymes (n = 1), and diarrhea (n = 1). All patients had received prior surgery, radiation, and chemotherapy before starting an IDH inhibitor. Median overall survival (OS) was not reached. OS after IDH inhibitor was 20.7 months and was longer in patients that had not received initial chemotherapy (p = 0.032). Median progression-free survival (PFS) was 6.8 months and was not different between tumor type, sex, or number of recurrences, but was longer in patients that did not receive initial chemotherapy (p = 0.041).

Conclusion: IDH inhibitors were well tolerated in patients with IDH-mutant HGG previously treated with DNA-damaging agents. A median PFS longer than 6 months is encouraging in this patient population and may be due to antitumor activity of IDH inhibitors in recurrent HGG.

Keywords: High-grade glioma; IDH inhibitors; IDH mutation; Recurrent.