TOPLINE:

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at treatment completion provides superior prognostic accuracy compared with PET in large B-cell lymphoma. The CLARITY assay demonstrates a negative predictive value exceeding 90% for predicting relapse when applied at the end of treatment.

METHODOLOGY:

• Researchers combined data from five clinical trials of frontline anthracycline-based chemotherapy, creating a retrospective cohort of 137 patients with large B-cell lymphoma.
• Analysis utilized the Foresight CLARITY assay for detecting ctDNA-MRD in plasma circulating cell-free DNA, with both analytical and clinical validation performed.
• Investigators assessed ctDNA-MRD using phase variants as disease markers, which are pairs of somatic single-nucleotide variants occurring in close proximity on the same DNA fragment.

TAKEAWAY:

• The CLARITY assay demonstrated undetectable ctDNA-MRD at the end of therapy provided superior outcome discrimination compared with disease response evaluation by PET.
• Only 5.5% of patients with large B-cell lymphoma lacked sufficient phased variants for ctDNA-MRD tracking.
• Detectable ctDNA-MRD at the end of treatment, even without a concordant positive PET result, indicated a high risk for relapse.
• Undetectable ctDNA-MRD in the setting of a positive PET scan likely reflected a false-positive PET finding.

IN PRACTICE:

“Early detection of persistent disease is particularly valuable as patients with primary refractory large B-cell lymphoma may benefit from curative CD19-directed chimeric antigen receptor T-cell therapy,” the authors of the study wrote.

SOURCE:

This study was led by Davide Rossi, MD, PhD, Clinic of Hematology, Oncology Institute of Southern Switzerland in Bellinzona, Switzerland. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

According to the authors, this study had several key limitations including its retrospective and exploratory nature, recruitment of heterogeneous populations based on sample availability, lack of central PET review, and insufficient power to formally test whether ctDNA-MRD improves diagnostic accuracy compared with PET. Additionally, approximately half of the patients enrolled across the five trials could not be assessed for ctDNA-MRD at the end of treatment due to missing samples.

DISCLOSURES:

Rossi disclosed ties with AbbVie, AstraZeneca, Janssen, and Roche.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.