1051 Blood-Based Diagnosis, Prognostication, and Monitoring of IDH Mutant Gliomas

INTRODUCTION: Glioma represents the most common CNS neoplasm in adults. Current classification utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic and therapeutic protocol groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and may not fully reflect the heterogeneous and evolving tumor landscape. METHODS: Initial optimization included, comparing the sensitivity of detection in RNA compared to DNA across different sample types. Following nucleic acid selection, key variables were optimized to enhance the signal-to-noise ratio using droplet digital PCR (ddPCR) technology and included: (i) amplicon size, (ii) cycling conditions, (iii) preamplification PCR, and (iv) gating threshold. RESULTS: Rigorous, blinded validation testing was performed in n = 133 patients comprising of IDH1.R132H gliomas (n = 80), IDH1 wild-type gliomas (n = 44), and age matched healthy controls (n = 9). Results from plasma based diagnostic testing yielded an overall sensitivity of 75.0% (95% CI: 64.1%-84.0%), specificity 88.7% (95% CI: 77.0%-95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. Findings indicated a correlation between IDH1.R132H mutant allele frequency (MAF; tumor tissue, plasma) and important clinical variables including: (i) overall survival, (ii) tumor shedding rate, (iii) treatment outcomes. Longitudinal monitoring using the mt-IDH1dx assay (n = 8, 39 timepoints) demonstrated excellent concordance with radiological findings and varying disease outcomes (progression, stable disease, treatment response). CONCLUSIONS: In addition to baseline diagnosis, mt-IDH1dx assay can be utilized for blood-based prognostication and longitudinal monitoring. The proposed workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling.