2651 - Outcomes for Patients with High-Risk IDH-Mutant Grade 2 Gliomas Treated with IDH Inhibitors
Presenter(s)
J. Pearce1, A. Basak1, S. Perni1, C. Wang2, T. Beckham2, T. A. Swanson1, W. Jiang Jr1, D. N. Yeboa1, M. F. F. McAleer1, C. Chung1, S. L. McGovern3, A. J. Ghia1, J. Li1, M. C. Tom1, M. Gubbiotti4, R. Eldaya5, C. Ene6, A. Patel7, and B. De2; 1Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of CNS Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Anatomical Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Neuroradiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Houston, TX, 7Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Post-resection radiotherapy (RT) is standard treatment for patients with high-risk IDH-mutant grade 2 (G2) gliomas. IDH inhibitors (IDHi) delay progression among patients with gross disease when compared with placebo, but real-world characterization of outcomes after their use remains limited. This study evaluates freedom from progression (FFP), patterns of relapse, and salvage therapy in patients with high-risk G2 gliomas treated with IDHi after initial maximal safe resection (MSR).
Materials/Methods: We performed an IRB approved single-institution retrospective review of 23 consecutive patients with IDH-mutant G2 gliomas treated with IDHi after MSR between 2020 and 2024. Kaplan-Meier method was used to estimate FFP. Among patients who progressed on IDHi, pre- and post-treatment gross tumor volumes (GTV) and FLAIR hyperintense volumes were compared using Fisher’s exact test. For comparison, FFP was calculated in a non-matched cohort of 60 patients treated with MSR followed by RT and sequential chemotherapy.
Results: Median follow up among patients receiving IDHi was 9 months (95% confidence interval [CI] 5-13). Median age was 32 years (CI 24-38) and all had Karnofsky Performance Status = 90. The most common histology was astrocytoma (78%). Median pre-operative tumor maximal dimension was 4.6 cm (interquartile range [IQR] 2.9-5.6). Following gross total resection (48%), subtotal resection (48%), or biopsy (4%), median latency to treatment with IDHi was 18 months (IQR 8-47). Patients were treated with vorasidenib (61%), ivosidenib (13%), or both agents sequentially (26%) for a median duration of 7.8 months (IQR 4.0-23.4).
Five patients (22%) treated with IDHi progressed at a median 4 months (range, 3-7) requiring re-resection (n=2) and/or RT (n=4); one was maintained on IDHi. All patients had progression confluent with prior disease (within 1 cm). Of re-resected patients, one remained G2 and another progressed to G4 at recurrence. Three patients had new FLAIR hyperintensity crossing midline at time of progression. Among patients who progressed on IDHi, GTV increased a median 22% (range 7-124%; P<0.001) and FLAIR hyperintense volume increased a median 68% (range 21-134%; P<0.001). Of patients treated with salvage RT, none had progressed at median follow up of 5 months (range 4-27). FFP following IDHi initiation was 79% (CI 54-92%) at 6 months, 73% (CI 46-88%) at 12 months, and 73% (CI 46-88%) at 24 months. In the non-matched RT cohort, FFP was 98% (CI 88-100%) at 6 months, 95% (CI 85-98%) at 12 months, and 89% (CI 78-95%) at 24 months.Conclusion: There may be a subset of high-risk G2 glioma patients for whom use of IDHi after MSR is not a durable treatment strategy. Disease and treatment volumes at progression for these patients may be larger at eventual RT. Future studies are warranted to characterize this subset further to identify patients for more prompt consideration of RT.