Diana Shi, MD

Vorasidenib, a mutant IDH inhibitor, is becoming part of standard treatment for IDH-mutant glioma. However, because these inhibitors are not curative, many patients receive subsequent radiation and chemotherapy.

Until now, it has been unclear whether treatment with vorasidenib before chemoradiation changes the effectiveness of these later therapies. 

To study this increasingly common treatment sequence, researchers at the Mass General Brigham Cancer Institute, Children’s Medical Center Research Institute at UT Southwestern, and the Broad Institute of MIT and Harvard—including lead authors Diana Shi, MD, and Ester Calvo Fernández, PhD, along with senior authors Mario Suvà, MD, PhD, and Samuel McBrayer, PhD—developed a genetically engineered mouse model of IDH-mutant astrocytoma that responds to vorasidenib.  

Mario Suvà, MD, PhD

They found that mice that received vorasidenib before chemoradiation lived longer than those treated with chemoradiation alone. Tumor cell analyses showed that vorasidenib promoted differentiation toward mature cell states, a shift that may help explain the improved response.  

The researchers also reported early outcomes from 29 patients with IDH-mutant glioma who received vorasidenib or ivosidenib prior to radiation with or without chemotherapy. Although follow-up was limited, only two patients experienced disease progression after radiation at the time of analysis. 

These findings suggest that prior treatment with a mutant IDH inhibitor does not reduce the effectiveness of chemoradiation and may, in fact, enhance it, supporting further evaluation of this treatment sequence in patients with IDH-mutant glioma. 

Published in Science Translational Medicine on August 5, 2026 | Read the paper: “Vorasidenib improves response to subsequent chemoradiation in a genetically engineered mouse model of IDH-mutant glioma” 

Summary reviewed by: Diana D. Shi, MD, co-first author; Mario L. Suvà, MD, PhD, co-senior author