A multicenter analysis has found that circulating tumor DNA (ctDNA) can serve as a sensitive biomarker for detecting measurable residual disease (MRD) following frontline treatment for large B-cell lymphoma.
The study, published in the Journal of Clinical Oncology, analyzed plasma samples from 137 patients enrolled across five prospective trials. Patients received anthracycline-based chemoimmunotherapy, with some protocols incorporating additional agents such as acalabrutinib or tafasitamab. Tumor-specific phased variants were identified from pretreatment samples and used to track ctDNA in 409 serial plasma specimens during and after therapy.
By the end of treatment, ctDNA was undetectable in 78 percent of patients. The presence of ctDNA at the end of therapy was associated with significantly worse outcomes: the 2-year progression-free survival (PFS) was 29 percent for patients with detectable ctDNA, compared with 97 percent for those without. Detection of ctDNA after just two treatment cycles also stratified risk (2-year PFS: 67 percent vs 96 percent).
When compared to positron emission tomography (PET) response criteria, ctDNA detection was found to have higher prognostic utility. Among patients with negative PET scans, ctDNA status remained predictive of relapse risk. Patients with undetectable ctDNA and negative PET scans had a 2-year PFS of 98 percent, while those with detectable ctDNA despite negative PET scans had a 2-year PFS of 31 percent.
The ctDNA assay used in the study employed phased variant enrichment and sequencing (PhasED-Seq), allowing for detection of mutant alleles at concentrations as low as one in one million cfDNA molecules. This sensitivity enabled earlier detection of molecular relapse in some cases, including instances of progression up to 18 months post-therapy.
Limitations of the study include relatively short follow-up for late relapse events and a small proportion of patients for whom MRD tracking was not possible due to low baseline ctDNA or insufficient phased variants.
The authors note that ongoing clinical trials are investigating the utility of ctDNA-guided treatment intensification or de-escalation strategies in large B-cell lymphoma.
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