NCOG-62. Real-world use of IDH inhibitors in a Broad IDH-mutant Glioma Population

BACKGROUND Mutant isocitrate dehydrogenase inhibitors (IDHi) have been well-studied in low-grade non-enhancing IDH-mutant (IDHm) gliomas. More work is needed to assess real-world outcomes of IDHi in a wider population of IDHm glioma patients. METHODS We collected clinical and radiographic data from IDHm glioma patients treated with IDHi from 2022-2025 at the Stanford Brain Tumor Center. RESULTS 36 IDHm glioma patients were treated with IDHi. Median age at diagnosis was 42.5 years. Majority of tumors were non-enhancing (n=29). There were 27, 6, and 3 patients with grade 2, 3 and 4 tumors, respectively. Over half (52.8%) of patients received prior chemoradiation, and 8 patients (22.2%) had concurrent treatment. Patients were treated with vorasidenib (n = 21), ivosidenib (n=14), or enasidenib (n=1). Over a median follow up time of 7.3 months, 26 patients were censored at data cut off, and mPFS and mOS were not reached. Best overall response by RANO 2.0 criteria for evaluable patients (n=33) was partial response in 2 patients (6.1%), stable disease in 25 patients (75.8%) and progressive disease in 6 patients (18.2%). Stable disease was achieved in patients with prior therapy (71%) and in grade 3 and 4 tumors (80% and 66.7% respectively). Enhancing disease was associated with worse BOR versus non-enhancing disease. 97.2% of patients experienced at least 1 IDHi adverse event with fatigue and transaminitis occurring in 76% and 43% of patients on vorasidenib compared to 0% and 14% of patients on ivosidenib respectively. CONCLUSION Clinical utility of IDHi in patients with higher grade IDHm gliomas, enhancing disease, and prior chemoradiation has not been well-studied. This retrospective analysis illustrates real-world outcomes, suggesting IDHi treatment may be considered for a broader range of IDHm gliomas. Adverse events are common but well-tolerated. Additional prospective studies are needed to better understand IDHi usage in the larger treatment paradigm.