Liquid Biopsy Newsletter
June 2026, Vol. 4
Dear Readers, dear Colleagues,
The evidence supporting ctDNA-based minimal residual disease (MRD) diagnostics continues to grow each month. This was confirmed once again at the EHA2026 Congress in Stockholm, where I was a speaker. We will share more about this in our next newsletter.
In this issue, we turn to Hodgkin lymphoma (HL) and share results we are particularly proud of: Our study on MRD assessment in the GHSG HD21 trial has now been published in Blood, one of the most respected journals in hematology.
The results are compelling. Using LymphoVista, our validated ctDNA sequencing assay, we were able to identify, after just two cycles of chemotherapy, which patients are at high risk of relapse and which are not. This kind of early signal has real consequences for how treatment can be planned and adjusted.
The study also demonstrates a key limitation of the current standard: PET imaging has a substantial false-positive rate, and ctDNA-MRD assessment addresses this directly.
When combined with PET, ctDNA-MRD allows clinicians to separate patients at very low risk of relapse from those at genuinely high risk, with direct implications for treatment decisions.
This is the kind of precision that LIQOMICS was built to deliver. LymphoVista is designed for exactly this use case, and the HD21 data provide strong clinical validation. The evidence we provide here adds to the growing body of evidence for ctDNA-MRD in hematological and solid tumors. We noted one example in Newsletter Vol. 3: The IMvigor011 trial showing that ctDNA-MRD-guided treatment can select bladder cancer patients who will benefit from adjuvant immunotherapy. The direction is consistent: ctDNA-MRD works, and it can protect patients from both under- and overtreatment.
Engaging with you, our readers and colleagues, is very important to us. That is why we are launching a regular series of online meetings on June 24, where you can interact with us directly. You can find the dates and register here: LINK
We look forward to hearing your thoughts and continuing this conversation with you.
Warm regards,
Sven Borchmann MD, PHD, LIQOMICS founder and Managing Director
Early Risk Stratification in Hodgkin Lymphoma: LymphoVista Validated in a Phase III Trial
What is Hodgkin Lymphoma and Why Does Treatment Monitoring Matter?
Hodgkin lymphoma (HL) is a cancer of the lymphatic system that most commonly affects young adults. Modern treatment regimens are highly effective, and the majority of patients achieve long-term remission. However, a meaningful proportion experience relapse or progression, and current therapies carry significant short- and long-term toxicities including cardiac damage, infertility, and secondary cancers.
The central challenge in treating HL is individualisation: how do you reduce treatment intensity for patients who have already responded well, while escalating for those who have not? And how do you make that decision early enough to matter?
Until now, the primary monitoring tool has been PET imaging after two cycles of chemotherapy (PET-2). Its false-positive rate is substantial: many patients with a positive PET-2 result are already in full remission and may receive unnecessary additional chemotherapy.
The GHSG HD21 Trial and the Role of MRD-2
The German Hodgkin Study Group (GHSG) HD21 trial is one of the most important prospective clinical trials in advanced Hodgkin lymphoma. It compared two intensive chemotherapy regimens, BrECADD and eBEACOPP, in over 1,400 patients. Treatment intensity after the first two cycles was guided by PET-2 results.
The ctDNA-MRD substudy applied LymphoVista HL, a variant of the validated LymphoVista assay specifically developed for HL, to blood samples collected from consenting patients before treatment and after two cycles of chemotherapy. An enriched sample set was analyzed, including a random subset of all consenting patients in the trial and all patients who experienced relapse, progression or death. The ctDNA-MRD result at the second time point after two cycles of chemotherapy is referred to as MRD-2.
After applying strict predefined quality criteria, 62 patients were eligible for the primary analysis: 16 (25.8%) were MRD-2 positive, 46 (74.2%) MRD-2 negative.
The Study Data in Detail
| Parameter | Result | What does this mean? |
|---|---|---|
| 4-Year Progression-Free Survival (PFS) in the enriched cohort | MRD-2 negative: 82.2% vs MRD-2 positive: 36.7% | Patients with detectable ctDNA after two cycles of chemotherapy had a markedly higher probability of relapse, progression, or death over four years. |
| Hazard Ratio for Progression, Relapse, or Death (MRD-2 positive vs. negative) | HR 5.3 (p = 0.0008) | MRD-2 positive patients had a 5.3-fold higher risk of a negative outcome compared to MRD-2 negative patients, a highly significant result. The effect was most pronounced in the BrECADD arm (HR 13.8), indicating that MRD-positivity after the most effective current treatment regimen identifies patients who are not sufficiently responding. |
| 4-Year PFS in PET-2 negative patients by MRD-2 status | MRD-2 negative: 93.3% vs MRD-2 positive: 50.0% | Even among patients with a negative PET-2 result, those who were MRD-2 positive had a substantially higher risk of relapse. MRD adds independent prognostic information beyond PET. |
| False-positive PET-2 results clarified by MRD-2 | 69.6% of PET-2 positive patients were MRD-2 negative | Among 23 patients with positive PET-2, 16 were MRD-2 negative. These patients likely received a higher treatment intensity than required. |
| 4-Year PFS by MRD-2 status in BrECADD-treated patients | MRD-2 negative: 88.0% vs MRD-2 positive: 17.1% (HR 13.8) | The strongest subgroup effect in the study. Among patients receiving the most effective current treatment regimen (BrECADD), MRD-2 positive patients had a 13.8-fold higher risk of relapse or death. These patients are not sufficiently responding despite optimal therapy and are the strongest candidates for treatment escalation or novel agents. |
The Decisive Finding: MRD-2 as an Independent Prognostic Tool
After just two cycles of chemotherapy, a single blood draw identifies patients at high risk and those likely to do well, regardless of PET result.
What does this mean in practice?
- MRD-2 negative: Patient has responded well and is at low risk of relapse. These patients may be candidates for treatment de-escalation in future trial designs.
- MRD-2 positive: Patient has residual molecular disease. These patients are at substantially higher risk and may benefit from early incorporation of novel agents such as checkpoint inhibitors.
- PET-2 positive but MRD-2 negative: Nearly 70% of PET-positive patients in this study were MRD-negative. For these patients, the PET result is likely a false alarm.
For patients: A blood sample taken after the second chemotherapy cycle provides a precise, non-invasive picture of treatment response, helping doctors adjust the plan before the consequences of under- or overtreatment accumulate.
Why This Study Matters Beyond Hodgkin Lymphoma
The GHSG HD21 substudy is the first study to assess MRD-2 using a validated genotyping and MRD assay with predefined quality criteria in patients treated on a prospective international phase III trial. This matters for two reasons.
First, LymphoVista HL met the validation standard required for clinical use and is now available as an in-house IVD. Second, the study demonstrates that ctDNA-MRD assessment and PET are complementary. Neither replaces the other. Combining MRD-2 with PET-2 identifies patients at very low and very high risk of relapse. This dual-biomarker approach is exactly the kind of precision medicine framework that will shape future HL trials.
These findings build directly on the platform LIQOMICS has established across lymphoma subtypes. The same logic that now underpins NCCN recommendations for LBCL (Newsletter Vol. 1) and treatment guidance in solid tumors through IMvigor011 (Newsletter Vol. 3) applies here: ctDNA-MRD is not a research tool. It is a decision tool for physicians and their patients.
LymphoVista: Validated MRD Assessment for Hodgkin Lymphoma
LymphoVista HL was specifically developed for patients with Hodgkin lymphoma. It achieves a limit of detection of 6.54 x 10-6 (approximately 6 ctDNA molecules among 1,000,000 total cfDNA molecules) from a standard blood draw of 10 mL. This sensitivity makes it capable of detecting residual disease at the earliest clinically relevant time points.
The GHSG HD21 results support the introduction of LymphoVista HL into routine care for selected patients and will inform the design of the next generation of treatment guidance trials in HL.
Sources:
- Heger JM, Mattlener J, Kaul H, et al. MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay. Blood. 2026;147(19):2194-2202.
- Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial. Lancet. 2024;404(10450):341-352.
- liquidbiopsyinfo.com: MRD evidence summary for Hodgkin lymphoma and beyond: www.liquidbiopsyinfo.com
More Information: liqomics.com/en/lymphovista | Personal consultation: contact@liqomics.com
