2079 - Assessment of IDH-Mutated Glioma Treatment Response to Long-Term Targeted Therapy by Longitudinal Tumor Volume Measurements

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 9

POSTER

Presenter(s)

Lindsey Ross, MD - Johns Hopkins Hospital, Baltimore, MD

L. G. Ross¹, D. Ross², P. Sriya³, R. Agyekum², P. Huang⁴, H. I. Sair⁵, J. Laterra¹, K. J. Redmond⁶, D. Kamson⁷, L. R. Kleinberg², and S. Puri⁸; ¹Johns Hopkins, Baltimore, MD, ²Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ³Johns Hopkins University, Baltimore, MD, ⁴Department of Oncology - Biostatistics and Bioinformatics Division, Johns Hopkins University School of Medicine, Baltimore, MD, ⁵Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, ⁶Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, ⁷The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, ⁸Oregon Health Science University, Portland, OR

Purpose/Objective(s):

Astrocytomas and oligodendrogliomas are characterized by a mutation in Isocitrate Dehydrogenase (IDH). Treatments include maximal safe surgical resection followed by observation, or radiation and chemotherapy (chemoRT). Vorasidenib (Vora), a dual mutant IDH1 and IDH2 inhibitor was recently FDA approved for recurrent IDH mutant (mIDH) glioma after demonstrating an improvement in progression free survival. Ivosidenib (Ivo), an mIDH1 inhibitor has also been used for mIDH glioma treatment. Long-term efficacy of mIDH inhibitors (mIDHi) as an alternative to chemoRT for progressive tumor has not been reported and thus we sought to assess treatment response through MRI tumor volumes (TVs) for patients being treated with long-term Ivo therapy. We hypothesize that long-term treatment with Ivo will result in a longitudinal decrease in TV.

Materials/Methods:

We retrospectively reviewed records from patients with mIDH glioma who were treated with mIDHi therapy. Adult patients treated with Ivo for >36 months were included. MRIs were reviewed from 1 year prior to starting Ivo therapy until the most recent scan. Tumors were manually contoured and 3D TVs were calculated on T2 FLAIR sequences using segmentation software in RayStation. TVs were analyzed using descriptive summary statistics.

Results:

Forty-nine patients with mIDH glioma had mIDHi treatment initiated between 2019 and 2024; 46 were treated with Ivo, 3 with Vora. Thirty-four patients in this cohort currently remain on mIDHi therapy, 13 of whom were on treatment for >36 months at the time of analysis and were included. All these patients had mIDH1 glioma and were treated with Ivo. Eleven patients had astrocytoma (9 grade 2 and 2 grade 3) and 2 had oligodendroglioma (both grade 2). Median age was 39.3 years (range 27.6-56.5 years). Twelve of 13 (92%) patients were male. Median duration of treatment was 59.5 months (range 37.4 to 79.3). Four of 13 (31%) had a prior history of radiation therapy, 3 of 13 (23%) had been treated with chemotherapy (2 with temozolomide, 1 with PCV). The mean number of scans evaluated was 9.4 (range 7-15). The mean reduction in TV was 9.3% from the scan prior to beginning Ivo until the most recent scan. Nine of 13 (69%) had an overall reduction in TV; all had radiographically stable disease with less than 35% volume reduction. Three patients had <20% increase in TV and 1 had a 43% increase in TV.

Conclusion:

Most patients (12 of 13, 92%) who remain on long-term Ivo for greater than 36 months had radiographically stable disease; one patient had progressive disease after 36 months of treatment with Ivo. Based on results from this small cohort, long-term Ivo therapy may help to control tumor growth longitudinally and delay the initiation of chemoRT for some patients. Future studies will seek to further define long-term impact of mIDHi therapy on overall survival and role in delaying initial or repeat chemoRT.