To characterize the outcomes of patients with low grade gliomas who undergo next-line therapies following disease progression after IDH inhibition

IDH inhibitors (IDHi) have reshaped the treatment landscape for low-grade glioma (LGG), yet optimal strategies following IDHi treatment failure remain unclear. We report the outcomes of next-line therapies in patients with IDH1-mutant LGG who progressed on ivosidenib.

Among 74 patients treated with ivosidenib monotherapy at our center, eight experienced progression per RANO criteria and subsequently received next-line therapy between October 2020 and October 2025. Clinical and imaging data, including volumetric tumor assessments, were analyzed. 

Patients (n=8) were 34–58 years old at the time of next intervention. Diagnoses included grade 2 astrocytoma (n=3) and oligodendroglioma (n=5). In addition to ivosidenib, prior treatments included maximal safe resection (n=7), temozolomide (n=4), and lomustine (n=1). Median time to progression on ivosidenib was 16 months (range 2–42). Next-line therapies included radiation therapy (RT) with concurrent temozolomide (n=4), re-resection plus chemoradiation (n=1), RT alone (n=1), and lomustine monotherapy (n=2). Post-treatment imaging showed radiographic improvement in five patients, stable disease in two, and treatment-related changes in one. Volumetric analysis revealed a median 42% tumor reduction 3–6 months following next interventions. Median tumor-specific growth rates decreased from +5.0% to –8.2% per month pre- vs post-intervention. At last follow-up (range 18.3-110.9 months), six patients maintained tumor control with clinical and radiographic stability. Two patients had disease progression, both of whom had high-risk features including no prior resection, tumor transformation, and poor chemotherapy tolerance.