Dordaviprone in H3K27M-mutant diffuse midline glioma: an editorial on emerging targeted therapy

Diffuse midline glioma (DMG) with H3K27 mutation is a highly aggressive grade 4 tumor with poor prognosis and limited treatment options. Dordaviprone, a first-in-class oral imipridone, recently received Food and Drug Administration approval for pediatric and adult patients with H3K27M-mutant DMG. In pooled analyses, it demonstrated meaningful clinical activity, with an overall response rate of up to 30% and durable disease control, particularly when administered after radiotherapy. Mechanistically, it targets the dopamine receptor D2 and ClpP, inducing apoptosis through both metabolic and epigenetic pathways. Treatment was well tolerated, with only grade 1-2 adverse events reported. Larger randomized studies are needed to validate efficacy and long-term safety.