A large Dutch study validates that a simple blood test can more accurately identify which patients with Large B-Cell Lymphoma (LBCL) are at risk of relapse after treatment. Last week, these results been published in The Journal of Clinical Oncology (https://doi.org/10.1200/JCO-25-01712).

Collaboration

The study, conducted by the HOVON–IKNL research group and led by PhD candidate Steven Wang and internist-hematologist Prof. Dr. Martine Chamuleau (both Amsterdam UMC – Cancer Center Amsterdam) was carried out in collaboration with Foresight Diagnostics, a Stanford University spin-off. The researchers evaluated a highly sensitive blood test that detects circulating tumor DNA (ctDNA) — tiny fragments of cancer DNA that can remain in the blood after treatment.

More precise measure

Today, doctors mainly rely on PET-CT scans to determine whether treatment has been successful. However, PET-CT scans can sometimes give unclear results. The ctDNA-based measurable residual disease (MRD) test aims to provide a more precise measure of whether any cancer remains.

Striking difference

The study followed a real-world cohort of newly diagnosed LBCL patients treated with standard therapy in nearly 50 hospitals across the Netherlands. Samples were processed in the Liquid Biopsy Center at Cancer Center Amsterdam (head A/Prof Dr Michiel Pegtel). At the end of treatment, 83% of patients had no detectable ctDNA (MRD-negative), while 17% still had detectable ctDNA (MRD-positive). The difference in outcomes was striking. Three years after treatment, only 17% of MRD-positive patients remained free of cancer, compared with 85% of MRD-negative patients.

ctDNA-MRD test outperforms standard methods

Importantly, the ctDNA-MRD test outperformed both PET-CT scans and the commonly used International Prognostic Index in identifying patients at high risk of relapse. It was able to detect high-risk patients in patients with positive PET-CT scans as well as among those whose PET-CT scans suggested a good response.

Implications for patient care

These findings suggest that adding ctDNA-MRD testing to routine care could help doctors better identify patients who need closer monitoring or additional treatment. In the future, this approach may support more personalized, risk-adapted treatment strategies and guide new clinical trials for patients with Large B-Cell Lymphoma.