Foresight Diagnostics Announces Publication of Landmark Study Demonstrating Prognostic Value of Ultrasensitive ctDNA-MRD Detection in Large B-Cell Lymphoma

BOULDER, Colo., Aug. 18, 2025 /PRNewswire/ -- Foresight Diagnostics, a leader in ultrasensitive minimal residual disease (MRD) detection, today announced the publication of a landmark pooled analysis in the Journal of Clinical Oncology demonstrating that MRD analysis using Foresight CLARITY™ at end of therapy provided greater prognostic accuracy than PET/CT in large B-cell lymphoma (LBCL). The findings highlight the potential of ultrasensitive MRD testing as a robust and reliable tool for remission assessment following frontline treatment.

The study integrated data from five prospective clinical studies and included 137 patients treated with curative-intent chemotherapy. MRD was measured using the Foresight CLARITY™ assay, which leverages PhasED-Seq™, a next-generation circulating-tumor DNA detection technology capable of identifying fewer than one mutant molecule per million.¹

Key findings from the study include:

• ctDNA-MRD assessment was prognostic as early as after two cycles of frontline chemotherapy. Patients with undetectable MRD after 2 cycles achieved a 2-year progression-free survival (PFS) of 96% compared to 67% for patients with detectable MRD (hazard ratio 6.9; p=0.0025).
  
  
• ctDNA-MRD assessment was most prognostic at end of therapy: 78% of patients were MRD-negative and had a 2-year PFS of 97%, compared to just 29% among MRD-positive patients (hazard ratio 28.7; p<0.0001). By comparison, PET/CT status at end of therapy was less predictive, with a hazard ratio of 3.6.
  
  
• MRD status further stratified risk within both PET-negative and PET-positive groups at end of therapy. Patients with detectable MRD faced a higher risk of relapse even if their imaging was negative. Conversely, PET-positive patients with undetectable MRD had significantly better outcomes than patients with both positive imaging and MRD results.
  
  
• Overall, Foresight CLARITY™ demonstrated 86% clinical sensitivity for relapse detection and 91% clinical specificity for remission at end of therapy, based on a median follow-up of 37 months.²

"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 Dr. David Kurtz, Chief Medical Officer at Foresight Diagnostics and co-author on the analysis. "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."

"Our study illustrates the potential of ctDNA-MRD detection to more precisely define remission in B-cell lymphoma," said Dr. Mark Roschewski, Senior Clinician and Deputy Branch Chief of the Lymphoid Malignancies Branch at the Center for Cancer Research and lead author of the publication. "The results support the incorporation of novel surrogate endpoints such as molecular response into prospective studies evaluating how they could aid clinical decisions following frontline therapy."

Ongoing trials are already evaluating ctDNA-guided treatment decisions in B-cell lymphoma. These include the ALPHA3 trial (NCT06500273), which is enrolling patients who achieve remission following frontline treatment but retain detectable ctDNA-MRD, and the SHORTEN-ctDNA study (NCT06693830), which is evaluating early ctDNA-MRD clearance as a potential marker to support frontline chemotherapy de-escalation.

Additionally, the results from this pooled analysis were included in Foresight's clinical recommendations to the National Comprehensive Cancer Network® (NCCN®) and supported the December 2024 update to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas, which incorporated ctDNA-MRD testing as a tool to adjudicate PET-positive end-of-therapy scans.³

The full manuscript, titled "Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma," is available online in the Journal of Clinical Oncology. These findings were previously presented at the 2023 American Society of Hematology (ASH) Annual Meeting and the 2023 International Conference on Malignant Lymphoma (ICML).

1 Klimova, et al. Oncotarget 2025.

2 Sensitivity – of the 22 patients with disease progression, 19 were MRD positive at the end of treatment. Specificity – of the 101 patients that did not progress, 92 were MRD negative at the end of treatment.

3 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed 21 July 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

About Foresight Diagnostics
Foresight Diagnostics is a privately held cancer diagnostics company and CLIA-registered laboratory. Its liquid biopsy platform, Foresight CLARITY™, is a novel assay that measures minimal residual disease (MRD) with reported detection limits in parts per million. The improved sensitivity of Foresight CLARITY™ has the potential to provide actionable information to physicians and biopharmaceutical companies to enable personalized treatment approaches for patients with solid tumor and hematologic malignancies. For more information, please visit foresight-dx.com and follow us on X, LinkedIn, and Bluesky.

SOURCE Foresight Diagnostics, Inc.