Real-world experience with vorasidenib in IDH-mutant gliomas: Tolerability, adverse events, and access in patients who did not meet INDIGO trial eligibility criteria.

e14029 Background: Vorasidenib was FDA-approved for the treatment of IDH-mutant grade 2 glioma in August 2024, largely on the basis of positive results from the phase 3 INDIGO trial, which excluded patients with grade 3 and grade 4 IDH-mutant gliomas and patients who had previously received chemoradiation. We evaluated the real-world use of vorasidenib in patients with IDH-mutant gliomas treated at our institution, focusing on treatment patterns, radiographic response, seizure control, tolerability, and access to vorasidenib for patients who did not meet the eligibility criteria for the INDIGO trial. Methods: Adult patients with IDH-mutant gliomas who started vorasidenib (40 mg/day) between September 5, 2024, and January 24, 2025, were included. Data collected included prior treatments, tumor grade and type, radiographic response, seizure control, adverse events, and insurance approval outcomes. Results: A total of 30 patients (median age: 45 years, range: 32–84) were included. Tumor types included astrocytoma (63%, n = 19), oligodendroglioma (33%, n = 10), and oligoastrocytoma (3%, n = 1), with tumor grades distributed as grade 2 (50%, n = 15), grade 3 (27%, n = 8), and grade 4 (23%, n = 7). Prior treatments included surgery (77%, n = 23), radiation therapy (90%, n = 27), chemotherapy (93%, n = 28) and targeted therapy with ivosidenib (77%, n = 23). Majority of grade 3 and grade 4 patients were heavily pretreated with temozolomide and bevacizumab. Median duration of vorasidenib treatment to date was 104.5 days (range: 8–141), with treatment ongoing in 28 patients. Radiographic response included 27 cases of stable disease and 3 cases of progressive disease. All progression was observed in grade 4 glioma patients. Seizure frequency was stable or improved in all patients. Vorasidenib was well-tolerated, with common toxicities including fatigue (37%, n = 11), headache (13%, n = 4), and transaminitis of any grade (23%, n = 7). Two patients discontinued treatment due to significant fatigue, and one transitioned back to ivosidenib. Insurance approval for vorasidenib varied by tumor grade with most grade 2 patients receiving initial approval (93%, n = 14) while 80% (n = 12) of grade 3/4 patients were initially denied coverage but were ultimately approved following an appeals process. Conclusions: Since August 2024 approval, vorasidenib has been used to treat patients who would not have qualified for the INDIGO trial. Though time on treatment is limited, our experience thus far indicates that the drug is fairly well-tolerated in this patient population, with 2/30 (6.7%) discontinuing treatment for fatigue. 27/30 (90%) of patients have had stable disease to date, and seizure frequency in all patients was stable or improved. Although insurance barriers were observed for higher-grade tumors, all patients successfully accessed treatment.