An accurate and rapid detection of minimal residual disease (MRD) after therapy could significantly improve management of diverse tumor types treated with curative intent. For example, standard therapies fail to cure 30-40% of patients with diffuse large B-cell lymphoma (DLBCL). In a July paper in Nature Biotechnology, Ludwig Stanford’s Ash Alizadeh and Maximilian Diehn and colleagues reported their development and assessment of a highly sensitive liquid biopsy technology— PhasED-seq (phased variant enrichment and detection sequencing)—for MRD detection in DLBCL and other tumor types. The new method uses multiple somatic mutations in individual DNA fragments to improve sensitivity, and the study showed it to be 40-100 times more sensitive than competing ctDNA detection approaches. In studying nearly 700 specimens from over 200 patients during therapy, PhasED-Seq detected nearly twice as many cases of MRD in patients with DLBCL as did a single nucleotide variant (SNV)-based ctDNA method. Applied to a group of 19 DLBCL patients who had completed all induction therapy with curative intent, PhasED-Seq detected MRD in every patient who relapsed, compared to a detection rate of just 40% using the alternative method. The team also used proof-of-concept studies in lung and breast cancers to highlight the promise of the method in other solid tumors.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).