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| Item Type: | Article |
|---|---|
| Title: | MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay |
| Creators Name: | Heger, Jan-Michel, Mattlener, Julia, Kaul, Helen, Ferdinandus, Justin, Schneider, Jessica, Schleifenbaum, Julia K., Schneider, Gundolf, Schaub, Valdete, Haenel, Mathias, Hellmuth, Johannes Christian, Dierlamm, Judith, Martin, Sonja, Mathas, Stephan, Meissner, Julia, Pegtel, D. Michiel, Zijlstra, Josée M., Ossowski, Anna, Becker, Kerstin, Hallek, Michael J., von Tresckow, Bastian, Borchmann, Peter and Borchmann, Sven |
| Abstract: | Beyond cure, major goals in patients with Hodgkin lymphoma (HL) are tailoring treatment to a patient’s individual risk for relapse to reduce acute and late toxicities, identifying candidates for early incorporation of novel agents, and making treatment affordable on a global level. Minimal residual disease (MRD) assessment by circulating tumor (ct)DNA sequencing emerged as a promising strategy to achieve these goals; however, previous studies differed in sampling timepoints, assay validation, and definitions for MRD negativity. Here, we applied LymphoVista – a validated ctDNA sequencing assay for genotyping and MRD monitoring in lymphoma – to samples obtained from the GHSG HD21 trial following two cycles of treatment (MRD-2) using a case-cohort-design. Patients with positive MRD-2 were at higher risk for relapse, progression or death compared with MRD-2 negative patients (4-year progression-free survival (PFS): 36.7% vs. 82.2%; HR 5.3, 95%CI 2.0-13.8; p = 0.0008). Following inverse probability weighting accounting for the number of events in the full reference set, patients with positive and negative MRD-2 had 4-year PFS rates of 72.2% vs. 95.3%. By combining MRD-2 with PET-2, patients were stratified into three distinct groups regarding risk of relapse: low (MRD-2 negative and PET-2 negative), intermediate (MRD-2 positive or PET-2 positive), and high (MRD-2 positive and PET2 positive). In summary, these results suggest that assessment of MRD-2 by LymphoVista allows for early outcome prognostication in patients with HL and could be used as a tool to improve treatment guidance on its own or in conjunction with PET-2. |
| Source: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology / Elsevier |
| Date: | 11 February 2026 |
| Official Publication: | https://doi.org/10.1182/blood.2025031089 |
| PubMed: | View item in PubMed |
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