Js05.7.a Early Seizure Control With [18f]-Dopa Pet Response After Idh Inhibition With Vorasidenib.

BACKGROUND Given the role of IDH mutations in epileptogenesis, the potential impact of IDH inhibitors on seizure control is of growing interest. However, as patients with a high burden of seizures were excluded from the INDIGO trial, timing and entity of seizure response after vorasidenib in a clinical setting are largely unexplored. The aim of this prospective study was to evaluate patterns and timing of seizure response in a real-world cohort of grade 2 IDH-mutant glioma patients treated with vorasidenib at our Institution. PATIENTS AND METHODS Patients with grade 2 IDH-mutant gliomas and non-enhancing residual tumour after surgery were enrolled in a vorasidenib Expanded Access Programme. Patients with persistent seizures, i.e. ≥1 unprovoked seizure within 30 days prior to treatment initiation, were identified. Seizures were recorded at the end of each 28-day cycle with a dedicated diary investigating several seizure aspects, including frequency, duration and patient-reported intensity. MRI and [18F]fluorodopa (F-DOPA) PET imaging were performed at baseline and every 3 cycles. RESULTS Between August 27, 2024 and April 21, 2025 45 patients were enrolled. Ten patients (6 astrocytomas and 4 oligodendrogliomas; median age 40.5 years) had persistent seizures at treatment initiation, with a mean seizure frequency during the 30 days prior to vorasidenib of 4.8/month (7 had levetiracetam monotherapy). Seven patients had measurable F-DOPA uptake at baseline (mean SUVmax, TBRmax and MTV: 3.2, 2.8, and 6.5 cm3). Over a median treatment duration of 6.6 months, 9/10 patients experienced seizure reduction without changes in antiseizure medication: 8/10 achieved early seizure freedom within 2 cycles, whereas one had gradual, sustained improvement over time. One patient only, after an initial improvement, experienced progressive worsening from cycle 3. Median duration of seizure response was 6.2 months. All patients showed stable disease per RANO criteria on conventional MRI at cycles 3 and 6, including the patient with seizure worsening (volumetric evaluation is ongoing). Among the 7 patients with measurable F-DOPA uptake at baseline, 6 who experienced seizure reduction also showed a trend toward metabolic response compared to baseline by cycle 3 (mean changes: SUVmax: -6.3%; TBRmax: -7.5%; MTV: -4.7 cm³) and 6 (SUVmax: -20.9%; TBRmax: -10.9%; MTV: -35.9 cm³), which traslated into 3 partial responses and 3 stable diseases according to RANO criteria 1.0. In contrast, the only patient who experienced seizure worsening showed a trend for an increased PET uptake by cycle 3. CONCLUSION In our study, vorasidenib was associated with early seizure control in patients with persistent seizures. Also, seizure improvement correlated with decreased F-DOPA PET uptake despite stable disease on conventional MRI, supporting the value of F-DOPA PET as a more sensitive tool for assessing treatment efficacy.