INNV-31. THE USE OF IVOSIDENIB IN PATIENTS WITH ENHANCING IDH1 MUTANT GLIOMAS
Minor, M; Ziv, MN; Patel, M; Johnson, M; Batich, K; Low, J; Shoaf, M; Khasraw, M; Desjardins, A; Friedman, H; Ashley, D; Peters, K
Published in: Neuro-Oncology
Ivosidenib offers a novel targeted therapy for non-enhancing IDH1 mutated gliomas following initial resection. Potential effects of IDH inhibitors on enhancing disease in clinical settings are not well established. This study characterizes a cohort of patients with IDH1 mutated gliomas with enhancing disease, who were initiated on monotherapy, off-label ivosidenib between October, 2020 to August, 2023. The cohort included 21 patients ages 29 to 73 years, 11 female and 10 male. Diagnoses represented were astrocytoma IDH1 mutant, grade 2-4 (N=9) and oligodendrogliomas IDH1 mutant, grade 2-3 (N=12). Prior treatment exposures included radiation therapy (N=11), temozolomide (N=15), bevacizumab (N=3), and treatment naïve (N=6). Time from diagnosis to ivosidenib initiation was 9.1±2.7 years. Although all patients had enhancing disease, ivosidenib was initiated due to non-enhancing disease progression (N=7), enhancing disease progression (N=13), and temozolomide intolerance (N=1). Size of enhancement by cross-section measured >1cm (N=15) and <1cm (N=6). Best radiographic responses per RANO criteria were partial response (N=3), stable disease (N=11), and progressive disease (N=7). At last contact, eleven patients were maintained on ivosidenib with no evidence of disease progression since initiation with an average treatment duration of 25.5±6.4 months and overall survival of 11.7±3.1 years. Ten patients had disease progression at median 5.2±3.1 months following ivosidenib initiation, three of whom died 16.7 (range 6.8-34.4) months after treatment initiation with an overall survival of 9.4 years (range 4.6-13.6). Adverse events from therapy included diarrhea (N=2), CK elevation (N=4), and QTc prolongation (N=2). No patients discontinued ivosidenib due to adverse events. No significant difference was detected between patients with and without disease progression due to size of enhancement (p=0.4) or prior treatment exposure (p=0.3). Future studies should include biopsies to understand the role of enhancing lesions in treatment response of IDH inhibitors.
