Key Clinical Summary:

• Idylla fusion assay showed high sensitivity (98.9%) and specificity (95%) for detecting ALK, ROS1, RET, NTRK, and MET fusions in lung cancer.
• MET exon 14 skipping detection achieved 100% sensitivity and specificity, outperforming traditional NGS.
• The automated, cartridge-based system provided faster turnaround and high success rates, particularly for surgical specimens.

A real-world evaluation of the Idylla fusion assay, an automated, cartridge-based real-time PCR platform, demonstrated rapid and reliable detection of targetable gene fusions in non-small cell lung cancer (NSCLC). The study highlights the assay’s clinical feasibility, accuracy, and efficiency compared with next-generation sequencing (NGS) methods, addressing common barriers such as long turnaround times and limited tissue availability.

Researchers prospectively analyzed 658 formalin-fixed, paraffin-embedded (FFPE) NSCLC samples, including 505 surgical specimens and 153 cytologic cell blocks, using the Idylla fusion assay. The assay detects ALK, ROS1, RET, NTRK1/2/3 fusions, and MET exon 14 skipping through a dual detection strategy: fusion-specific (FS) primers for known isoforms and expression imbalance (EI) analysis for partner-agnostic detection.

Of all samples tested, 96.2% produced valid results, 2.4% were invalid, and 1.2% had execution errors. Among valid tests, 70% were negative, 20% positive, and 6.4% equivocal. Surgical samples outperformed cytologic ones, with a 97% success rate vs 93% (P = .01). The mean tumor purity was 33.9% (SD = 17).

Performance analysis revealed excellent assay metrics, including sensitivity of 98.9%, specificity of 95%, positive predictive value of 78%, and negative predictive value of 99.8%. When focusing solely on FS detection, sensitivity ranged from 90 to 100% and specificity from 99.7 to 100%. EI-based results were less consistent, particularly for ROS1 (33.3%) and ALK (87.1%), but integrating FS and EI data improved accuracy to 100% sensitivity and 98% specificity.

Importantly, the MET exon 14 skipping assay achieved perfect sensitivity and specificity (100%), while data for NTRK1/2/3 were limited.

The Idylla fusion assay offers a streamlined, rapid alternative to NGS, enabling molecular testing in laboratories without extensive sequencing infrastructure. Its automation, minimal manual handling, and short turnaround support timely identification of actionable gene fusions critical for targeted therapy decisions in NSCLC.

Given its high accuracy and reliability, particularly for ALK, ROS1, RET, and MET exon 14 skipping, the platform is well suited for routine clinical use or reflex testing where NGS is unavailable or delayed. However, results derived solely from EI analysis should be confirmed by orthogonal methods to ensure diagnostic accuracy.

This prospective study validates the Idylla fusion assay as a rapid, accurate, and practical solution for detecting actionable fusions in lung cancer. With strong concordance to NGS and high assay performance, it represents a significant advance toward efficient molecular profiling and personalized lung cancer management.

Source:

Yakoub M, Pujadas E, Kim D, et al. Routine Implementation of the Idylla Fusion Assay: An Assessment of Performance Based on Prospective Reflex Testing of Non-Small Cell Lung Carcinoma in a Large Laboratory Setting. Presented at the 2025 AMP Annual Meeting & Expo. November 11-15, 2025; Boston, Massachusetts. ST045