Ivosidenib for the treatment of IDH1-mutant glioma, grades 2-4: Tolerability, predictors of response, and outcomes release_hdrk5274o5bbhahkrrnhgnc3hm

Abstract

Mutant isocitrate dehydrogenase (IDHm) inhibitors represent a novel targeted approach for treating IDHm glioma patients, yet their optimal use in clinical practice outside of clinical trials remains undefined. This study describes the real-world utilization of the mutant IDH1 inhibitor (IDHi), ivosidenib, in patients with IDHm glioma. We retrospectively reviewed clinical and radiographic data from patients with IDHm glioma treated with ivosidenib monotherapy from 2020 to 2024 at the Dana-Farber Cancer Institute and Massachusetts General Hospital. This cohort included 74 patients with a median age of 39. There were 35 astrocytomas and 39 oligodendrogliomas, with 49, 23, and 2, grade 2, 3, and 4 tumors, respectively. Nineteen patients (26%) experienced an adverse event, although only 1 patient discontinued ivosidenib for adverse events. Median progression-free survival was 31 months and median overall survival was not reached. Seven patients (9%) had partial response, 3 (4%) had minor response, 47 (64%) had stable disease, and 17 (23%) had progressive disease. The presence of enhancing disease at ivosidenib initiation was associated with lower disease control rates (DCR) whereas DCR differences were not detected based on grade (grade 2 vs. 3), tumor histology, or age. Subsequent-line ivosidenib use had lower DCR although this may have been explained by enrichment of patients with enhancing disease. In this large cohort of IDHm glioma patients, ivosidenib was well tolerated. Our results support the use of IDHi therapy in patients with grade 2 or 3 astrocytoma or oligodendroglioma and highlight limited effectiveness in patients with enhancing disease.
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