# Evaluation of an IDH1/2 Mutation FastTrack Assay for Patients with Cholangiocarcinoma

## TL;DR

This study compares two methods for detecting IDH1/2 mutations in cholangiocarcinoma patients, finding that a fast assay works well for routine use while NGS provides more detailed genetic data.

## Contribution

The study evaluates the Idylla™ IDH1-2 Mutation Assay Kit as a rapid diagnostic tool for IDH mutations in cholangiocarcinoma, comparing it to NGS.

## Key findings

- IDH1/2 mutations were detected in 68% of cases using both Idylla™ and NGS with high concordance.
- Idylla™ detected no mutations in two samples where NGS found mutations.
- Idylla™ is recommended for routine diagnostics due to its speed and ease of use.

## Abstract

Cholangiocarcinoma, a malignancy of the bile ducts, is challenging to treat due to late diagnosis and limited options. Advances in molecular genetics enable personalized approaches, including targeting isocitrate dehydrogenase (IDH) mutations, found in some cholangiocarcinoma patients. IDH1 inhibitor Ivosidenib has shown efficacy in clinical trials, offering new hope for patients with IDH1-mutant cholangiocarcinoma. Standardized testing protocols are vital for consistent and accurate mutation detection. In this study we established the Idylla™ IDH1-2 Mutation Assay Kit and evaluated the results compared to Next-Generation Sequencing (NGS), a key tool for molecular characterization. Idylla™ provides a rapid, user-friendly method for IDH1/2 mutation detection, suited to immediate clinical needs. Meanwhile, NGS delivers comprehensive genetic profiles, valuable for personalized medicine and research, albeit with higher cost and longer processing times. Choosing between these methods depends on clinical context, resources, and patient-specific needs.

Background: Cholangiocarcinoma, a malignancy originating from the bile ducts, poses significant treatment challenges due to its typically late diagnosis and limited therapeutic options. However, recent advances in molecular genetics enable more personalized treatment approaches. A notable breakthrough in this context is the identification of isocitrate dehydrogenase (IDH) mutations, particularly IDH1 and IDH2, which occur in a subset of cholangiocarcinoma patients. Those with IDH1/2 mutations may benefit from targeted therapies. For instance, Ivosidenib, an IDH1 inhibitor, has shown efficacy in clinical trials, offering a new therapeutic option for patients with IDH1-mutant cholangiocarcinoma. Developing and implementing standardized protocols for testing and reporting mutation status are crucial for consistency and accuracy in clinical practice. Both the Idylla™ IDH1-2 Mutation Assay Kit as a FastTrack method and Next-Generation Sequencing (NGS) panels play critical roles in molecular characterization of cholangiocarcinoma. Methods: Under this aspect, a set of cholangiocarcinomas was tested using the Idylla™ platform regarding the respective recommended guidelines and standards of DIN EN ISO:17020 and DIN EN ISO:15198. Results: Overall, 25 clinically diagnosed intrahepatic cholangiocarcinomas or Adeno-CUPs were analyzed. IDH1/2 mutations were identified in 68% (17/25) of cases using both methods, with high concordance between NGS and Idylla™ results. Discrepancies were observed in two samples, where Idylla™ detected no mutations, but NGS reported IDH1 and IDH2 mutations, respectively. Conclusions: IdyllaTM offers a rapid, user-friendly, and specific method for detecting IDH1/2 mutations, ideal for immediate clinical needs. NGS, while more time-consuming and costly, provides comprehensive genetic profiles valuable for personalized medicine and research. The choice between these methods should be guided by the clinical context, resource availability, and individual patient needs. For routine diagnostics, we recommend an algorithmic approach starting with the FastTrack method followed by NGS for wildtype cases.