Landmark Study Highlights Prognostic Value of Liquid Biopsy in Large B-Cell Lymphoma

A new study published in the Journal of Clinical Oncology demonstrates that a highly sensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) assay offers superior prognostic value compared to traditional imaging in patients with large B-cell lymphoma (LBCL).^1,2 This landmark research, a collaboration between Foresight Diagnostics and multiple clinical sites, validates the use of Phased variant Enrichment and Detection Sequencing (PhasED-Seq) ctDNA testing to guide clinical decisions and stratify risk.

“These findings highlight the clinical value of achieving ctDNA-MRD negativity at the end of treatment and underscore the limitations of relying solely on PET/CT for remission assessment,” said David Kurtz, MD, chief medical officer at Foresight Diagnostics and co-author on the analysis, in a press release.² “With the ultra-high sensitivity of Foresight CLARITY, we can detect disease that imaging misses, offering clinicians a more accurate and actionable tool for post-treatment risk stratification.”

A New Gold Standard for Prognosis

The analysis pooled data from 5 prospective clinical studies, encompassing 137 patients treated with curative-intent chemotherapy. A key finding was the ability of ctDNA-MRD assessment to predict patient outcomes as early as after just 2 cycles of treatment. The most significant prognostic value, however, was observed at the end of therapy. At this point, patients who were MRD-negative had an impressive 2-year progression-free survival (PFS) rate of 97%, in stark contrast to the 29% PFS for those who remained MRD-positive.

This finding represents a significant advancement over standard imaging. The study showed that ctDNA-MRD status was more predictive of patient outcomes than end-of-therapy PET/CT scans. The ctDNA-MRD assessment was also able to further stratify risk within both PET-negative and PET-positive patient groups, suggesting it provides a more nuanced and accurate picture of a patient's remission status.

The Role of an Ultrasensitive Assay

The study utilized a personalized, patient-specific ctDNA assay, which is a key differentiator from other methods. This assay, marketed as Foresight CLARITY, demonstrated high clinical performance, with an 86% clinical sensitivity for detecting relapse and a 91% clinical specificity for confirming remission at the end of therapy. The high sensitivity of this assay allows for the detection of minute amounts of residual disease that might be missed by conventional imaging.

Impact on Clinical Practice and Future Guidelines

The implications of this study are profound for the management of LBCL. The ability to accurately identify patients at high risk of relapse using a blood-based test could lead to a paradigm shift in posttreatment surveillance and management. High-risk, MRD-positive patients could be candidates for closer monitoring or even novel consolidation therapies, while MRD-negative patients might be spared unnecessary imaging or interventions.

The findings have already had a tangible impact, with the data being used to support an update to the National Comprehensive Cancer Network (NCCN) Guidelines. The updated guidelines, as of December 2024, now incorporate ctDNA-MRD testing to adjudicate PET-positive end-of-therapy scans, providing clinicians with a validated tool to refine risk stratification and improve patient care. This represents a significant step towards the integration of liquid biopsy into routine oncology practice.

REFERENCES:

1. Roschewski M, Kurtz DM, Westin JR, et al. Remission Assessment by Circulating Tumor DNA in Large B-cell Lymphoma. J Clin Oncol. 2025 Aug 13:101200JCO2501534. doi: 10.1200/JCO-25-01534. Online ahead of print.

2. Foresight Diagnostics Announces Publication of Landmark Study Demonstrating Prognostic Value of Ultrasensitive ctDNA-MRD Detection in Large B-Cell Lymphoma. News release. Foresight Diagnostics. August 18, 2025. Accessed August 19, 2025. https://tinyurl.com/a3959ydu