Abstract 556: The Idylla™ IDH1-2 Mutation Assay Kit: A tool for mutation detection in <i>IDH1</i> and <i>IDH2</i> genes

Abstract Background: Mutations in the genes encoding isocitrate dehydrogenase (IDH1 and IDH2) are frequently detected in various cancers, including acute myeloid leukemia (~20%) and glioma (up to ~80%). They commonly involve a single amino acid substitution at codon R132 in IDH1, and R140 or R172 in IDH2 and are important for diagnosis and prognosis as well as therapeutic decisions. With advancements in molecular diagnostics and precision therapy, IDH inhibitors such as ivosidenib, vorasidenib and enasidenib are now mainstay in management of patients with a susceptible mutation. Methods: The Idylla™ IDH1-2 Mutation Assay Kit (RUO) is a fully automated qPCR assay for the qualitative detection of 15 common mutations in IDH1 (R132C/H/G/S/L) and IDH2 (R140Q/L/G/W, R172K/M/G/W/S) at codon level. The assay consists of a ready-for-use Idylla™ DNA Cartridge and an assay specific Idylla™ Vial. It runs on the Idylla™ Platform and covers the entire process from sample to result including specimen processing, real-time PCR amplification, detection, data analysis, and result reporting, within 100 minutes.Five clinical sites in US and Europe participated in an early access program to evaluate performance of the assay and establish a final classification algorithm by testing a total of 241 specimens, including FFPE, human whole blood and bone marrow samples, and extracted DNA from these sample types. Reference results were obtained using a range of established methods with different mutations in scope, such as Sanger sequencing, immunohistochemistry, NGS and qPCR. Results: Of 241 Cartridges, one invalid result was obtained, while 13 results were flagged as having low DNA input. Compared to available reference methods, overall concordance was 98.3% (235/239), 100% (140/140) and 99.6% (230/231) for IDH1 R132, IDH2 R140 and R172, respectively (see table). Conclusion: The Idylla™ IDH1-2 Mutation Assay Kit demonstrates a high concordance with established reference methods across a range of different specimen types. Reference method(s) PPA (%) NPA (%) OPA (%) MUT WT Total Idylla™ IDH1-2 Mutation Assay Kit IDH1_R132x 111 3 114 99.1 97.6 98.3 WT 1 124 125 Total 112 127 239 IDH2_R140x 10 0 10 100.0 100.0 100.0 WT 0 130 130 Total 10 130 140 IDH2_R172x 25 0 25 96.2 100.0 99.6 WT 1 205 206 Total 26 205 231 Total 148 462 610 Citation Format: Bram De Craene, Katrien Trappeniers, Ana Marcelino, Lee Robertson, Phillippe Taniere, Jo Van Dorpe, Malaïka Van der Linden, Maria Arcila, Khedoudja Nafa, Jochen K. Lennerz, Richard Craig Carson, Richard D. Ledding, Sofie Metsu. The Idylla™ IDH1-2 Mutation Assay Kit: A tool for mutation detection in IDH1 and IDH2 genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 556.