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Leo I. Gordon, MD, FACP

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Can ctDNA Analysis Be Used to Predict Outcomes in High-Risk DLBCL?

By: Vanessa A. Carter, BS
Posted: Friday, May 6, 2022

Sirpa Leppä, MD, PhD, of the University of Helsinki, and colleagues examined the translational significance of liquid biopsy of circulating tumor DNA (ctDNA) in patients with high-risk diffuse large B-cell lymphoma (DLBCL). Published in the journal Blood, these results revealed novel molecular determinants in liquid biopsy that have the potential to influence noninvasive treatment options.

“In light of the findings, the methods available for targeting therapies in aggressive lymphomas are insufficient, while those used to measure the efficiency of therapies are inaccurate,” stated Dr. Leppä in an institutional press release. “This can expose patients to overtreatment and unnecessary adverse effects and make it difficult to come up with therapies tailored to individual patients.”

The investigators discovered that ctDNA analysis uncovered hidden biologic and clinical heterogeneity. They also found that a high ctDNA burden appeared to determine an increased risk of relapse and death, although this was independent of conventional risk factors. Additionally, translationally relevant molecular, prognostic, and phenotypic information was discovered via genomic dissection of pretreatment ctDNA, which notably extended beyond diagnostic tissue biopsies.

The investigators noted that chemorefractory lymphomas were observed to exhibit diverging ctDNA kinetics during therapy. On the other hand, end-of-therapy negativity for measurable residual disease seemed to characterize cured patients; clinical issues, such as false residual positron-emission tomography positivity, appeared to be resolved.

“Fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, used machine learning to show that end-of-therapy fragmentation patterns predict outcome,” Dr. Leppä concluded. “ctDNA analyses will in the future revolutionize cancer diagnostics and clinical decision-making, but further research on the benefits of the findings is needed before ctDNA analyses of blood samples will become part of routine examinations for cancer patients.”

Disclosure: Disclosure information was not provided.


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