Ivosidenib off-label use for IDH mutant gliomas: The MD Anderson Cancer Center real life experience.

Abstract

e14022 Background: Ivosidenib, a small-molecule IDH inhibitor is FDA approved for relapsed or refractory acute myeloid leukemia and cholangiocarcinoma with IDH1 mutation. Early phase clinical trials have shown promising findings for IDH mutant gliomas and results of larger studies of IDH inhibitors in gliomas are still pending. Meanwhile, neuro-oncologists continue to encounter patients with IDH mutant gliomas with limited treatment options. Here, we describe our experience with off-label use of ivosidenib in IDH mutant gliomas. Methods: This is a retrospective case series study in a single cancer care institute. Data points collected include but not limited to patient demographics, type of IDH mutation, treatment history prior to starting ivosidenib, duration of treatment, and progression-free survival. Descriptive statistics were used to summarize patient’s characteristics. The distribution of median progression-free survival (mPFS) was estimated by the Kaplan-Meier method. Results: From August 2018 to December 2022, we identified 13 patients with IDH-mutant glioma prescribed ivosidenib 500mg daily off-label. Four patients did not receive treatment: two were too sick soon after ivosidenib prescribed, and two were not able to get financial coverage. For the nine patients that were treated, median age was 37 (range 25-44). 8 were males and 1 was female. Five have IDH1 R132H mutations, 1p19q intact and four have IDH mutation and 1p19q co-deletion. The highest grade for the tumor is grade 3. Four have non-enhancing disease only. The median lines of therapy prior to starting ivosidenib was 2 (range 0-5). Three patients did not have radiation by the time they started ivosidenib, including two who received this drug as first-line treatment initiated by providers outside of MD Anderson. All patients are still alive as of January 11th, 2023. Disease control rate (all stable disease) was 78%. After a median follow-up of 17.8 (range 15-29) months, mPFS was 3.81 (95% CI: 1.25, 12.78) months. Patients with non-enhancing disease had better PFS than those with enhancing disease, but this was not statistically significant (median PFS: 8.28 vs 3.81 months, p-value = 0.42). Two patients had adverse events: one with grade 1 lethargy, and another patient had a grade 3 surgical wound infection unrelated to the drug requiring a pause in treatment. Conclusions: Ivosidenib was successfully approved by third party payers for treatment of nine patients with IDH mutant gliomas. Ivosidenib was well-tolerated with a modest PFS. Patients with non-enhancing disease may trend toward better PFS than those with enhancing disease. The updated survival data and potential correlation with clinical, molecular, and radiographic data will be presented at the conference.