Marking a significant advancement for the diagnosis and treatment of non-Hodgkin lymphoma (NHL), researchers have validated the performance of the cobas® EZH2 Mutation Test, a companion diagnostic tool designed to detect specific gain-of-function EZH2 mutations. The study, led by Peter Schlag and his colleagues from Roche Molecular Systems, Inc., including Johnny Shyu, Sylwia Karwowska, Chitra Manohar, Huan Truong, and Guili Zhang, along with Dr. John Longshore from Carolinas Pathology Group, has been published in the peer-reviewed journal PLOS ONE.

The cobas®  EZH2 Mutation Test is designed to identify gain-of-function mutations in the EZH2 gene, which are prevalent in a significant portion of diffuse large B Cell Lymphoma (DLBCL) and Follicular (FL) cases. These mutations often correlate with high-grade cancer progression and poor prognosis. The test was developed in collaboration with Epizyme, Inc. an Ipsen company, and Eisai Co., Ltd., to support the clinical trials of tazemetostat, an epigenetic therapy targeting EZH2.

Peter Schlag stated, “The cobas® EZH2 Test demonstrated exceptional concordance with next-generation sequencing (NGS), underscoring its reliability and accuracy in detecting EZH2 mutations.” This high concordance rate was observed in both the technical performance verification (TPV) and clinical validation studies, which included hundreds of clinical samples.

The TPV study involved over a hundred commercially procured samples and reported an overall agreement > 98.1%  between the cobas® EZH2 Test and NGS for wild-type and mutation-positive EZH2. Similarly, the clinical validation study, which analyzed several hundred samples from the tazemetostat clinical trial, showed very high positive and negative percent agreement. These results demonstrate the test’s efficacy in a clinical setting, paving the way for its FDA approval in June 2020 as a companion diagnostic intended for the identification of follicular lymphoma patients with an EZH2 mutation for treatment with TAZVERIKTM (tazemetostat), in accordance with the approved therapeutic product labeling.          

Key findings from the validation study included the detection of single and rare double EZH2 mutations in both FL and DLBCL samples. The reproducibility study demonstrated the robustness of the test under various testing conditions, where accurate results for low percent mutation samples were reported with a remarkably low invalid rate.

Peter Schlag emphasized the clinical implications, stating, “The cobas® EZH2 Test provides a rapid and accurate method to identify patients who would benefit from tazemetostat, thereby improving personalized treatment strategies for FL patients.” 

The team of Peter Schlag also highlighted the broader impact of this diagnostic tool on precision medicine. By facilitating the identification of EZH2 mutations, the cobas® EZH2 Test plays a crucial role in the targeted therapy of NHL, aligning with the growing emphasis on personalized medicine in oncology.

In conclusion, the cobas® EZH2 Mutation Test represents a significant advancement in the diagnostic landscape of NHL, offering a reliable, efficient, and clinically validated tool for detecting EZH2 mutations. This breakthrough not only supports the targeted treatment of FL but also underscores the importance of integrating advanced diagnostics into personalized cancer care.

Journal Reference

Shyu, J. Y., Schlag, P. A., Karwowska, S. M., Manohar, C. F., Truong, H. M., Longshore, J. W., & Zhang, G. (2023). Performance of the cobas EZH2 mutation test on clinical samples from non-Hodgkin lymphoma patients. PLOS ONE. DOI: https://doi.org/10.1371/journal.pone.0292251

Lancet Oncol. 2020 November; 21(11): 1433–1442. DOI: https://doi.org/10.1016/S1470-2045(20)30441-1