Vorasidenib in IDH1/2 -mutant low-grade gliomas: a prospective study on volumetric MRI and seizure outcome

BACKGROUND: The IDH1/2 inhibitor vorasidenib demonstrated efficacy in residual or recurrent grade 2 IDH1/2-mutant gliomas after surgery. However, there is lack of knowledge regarding factors predicting the probability of response. PATIENTS AND METHODS: We conducted a prospective single-centre study on 54 grade 2 IDH1/2-mutant astrocytomas and IDH1/2-mutant 1p/19q-codeleted oligodendrogliomas treated with vorasidenib. MRI response (2D and 3D) and seizure outcome were longitudinally assessed. Factors associated with response were explored using regression models. RESULTS: With a median follow-up of 17.5 months, vorasidenib induced progressive tumour shrinkage on MRI, with median volume reductions of - 12.2% at cycle 6, -27.8% at cycle 12, and -55.5% at cycle 18. Best volumetric response was CR in 1 patient, PR in 5, MR in 9, SD in 31 and PD in 7. The ORR (CR + PR + MR) was 28%. Eighteen patients who had focal grade 3 areas showed similar volumetric response and ORR. 9/12 (75%) patients with baseline seizures achieved ≥50% reduction or seizure freedom. MRI response correlated with early treatment initiation and early seizure reduction. Vorasidenib was generally well tolerated, with liver enzyme elevation being the main adverse event. CONCLUSIONS: Vorasidenib induced sustained tumour shrinkage and seizure control. Early treatment initiation and early seizure reduction were associated with MRI response.