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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Hematologic Malignancies
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1407003

Tumor-informed ctDNA Assessment as a Valuable Prognostic and Predictive Biomarker in Diffuse Large B-cell Lymphoma

Provisionally accepted
Mayur Narkhede Mayur Narkhede 1*Sarah Tomassetti Sarah Tomassetti 2,3Madiha Iqbal Madiha Iqbal 4Antony Tin Antony Tin 5Samuel Rivero- Hinojosa Samuel Rivero- Hinojosa 5Giby V. George Giby V. George 5Hayley Widden Hayley Widden 5Ryan Benrud Ryan Benrud 5Meenakshi Malhotra Meenakshi Malhotra 5Angel Rodriguez Angel Rodriguez 5Minetta C. Liu Minetta C. Liu 5
  • 1 Department of Hematology Oncology, University of Alabama at Birmingham, Birmingham, United States
  • 2 Harbor–UCLA Medical Center, Torrance, California, United States
  • 3 David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
  • 4 Blood and Marrow Transplant and Cellular Therapy (CAR-T) Program, Mayo Clinic Florida, Jacksonville, Florida, United States
  • 5 Natera, Inc, Austin, United States

The final, formatted version of the article will be published soon.

    Background: A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment.Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification.Results: In total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy.ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.

    Keywords: Molecular residual disease, treatment response monitoring, circulating tumor DNA, nextgeneration sequencing, surveillance

    Received: 26 Mar 2024; Accepted: 02 Jul 2024.

    Copyright: © 2024 Narkhede, Tomassetti, Iqbal, Tin, Rivero- Hinojosa, George, Widden, Benrud, Malhotra, Rodriguez and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mayur Narkhede, Department of Hematology Oncology, University of Alabama at Birmingham, Birmingham, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.