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Updated: Feb 11, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay
Jan-Michel Heger1,2,3,4,5, Julia Mattlener1,2,5, Helen Kaul1,5
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.
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 DNA (ctDNA) sequencing emerged as a promising strategy to achieve these goals; however, previous studies differed in sampling time points, 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 German Hodgkin Study Group (GHSG) HD21 trial after 2 cycles of treatment (MRD-2) using a case-cohort design. Patients with positive MRD-2 result 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%; hazard ratio, 5.3; 95% confidence interval, 2.0-13.8; P = .0008). After inverse probability weighting accounting for the number of events in the full reference set, patients with positive and negative MRD-2 results had 4-year PFS rates of 72.2% vs 95.3%. Combining MRD-2 with positron emission tomography after 2 cycles of BrECADD/eBEACOPP (PET-2) can identify patients at very low and patients at very high risk of relapse, progression, or death. In summary, these results suggest that MRD-2 assessment 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.
Insights
Minimal residual disease (MRD) assessment using ctDNA sequencing after two treatment cycles in Hodgkin lymphoma (HL) patients effectively predicts relapse risk. This approach aids in personalizing therapy and improving outcomes.
Area of Science:
- Hematology
- Oncology
- Molecular Diagnostics
Background:
- Current Hodgkin lymphoma (HL) treatment aims to minimize relapse risk and toxicities.
- Minimal residual disease (MRD) assessment via circulating tumor DNA (ctDNA) shows promise for personalized treatment strategies.
- Previous MRD studies lacked standardization in timing, validation, and negativity definitions.
Purpose of the Study:
- To evaluate the LymphoVista ctDNA assay for MRD monitoring in HL patients post-two treatment cycles (MRD-2).
- To correlate MRD-2 status with patient outcomes, specifically progression-free survival (PFS).
- To explore combining MRD-2 with positron emission tomography (PET-2) for enhanced risk stratification.
Main Methods:
- Utilized the validated LymphoVista ctDNA sequencing assay on samples from the GHSG HD21 trial.
- Employed a case-cohort design analyzing MRD status after two treatment cycles (MRD-2).
- Applied inverse probability weighting to adjust for event numbers in the reference set.
Main Results:
- MRD-2 positive patients faced significantly higher relapse risk (4-year PFS: 36.7%) compared to MRD-2 negative patients (82.2%).
- Adjusted 4-year PFS rates were 72.2% for MRD-2 positive and 95.3% for MRD-2 negative patients.
- A three-tiered risk stratification was established by combining MRD-2 and PET-2 results: low, intermediate, and high relapse risk groups.
Conclusions:
- MRD-2 assessment by LymphoVista provides early and accurate outcome prognostication in HL.
- This ctDNA-based method can serve as a standalone tool or complement PET-2 for improved treatment guidance.
- Personalized risk assessment can lead to more tailored and effective Hodgkin lymphoma management.
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