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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: |
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  ORCID: https://orcid.org/0000-0001-9626-1413, 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. |
| Keywords: | Circulating Tumor DNA, DNA Sequence Analysis, Hodgkin Disease, Residual Neoplasm |
| Source: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology / Elsevier |
| Volume: | 147 |
| Number: | 19 |
| Page Range: | 2194-2202 |
| Date: | 7 May 2026 |
| Official Publication: | https://doi.org/10.1182/blood.2025031089 |
| PubMed: | View item in PubMed |
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