By: Kerri Fitzgerald
Following frontline treatment for large B-cell lymphoma (LBCL), ultrasensitive circulating tumor DNA (ctDNA) is more prognostic of disease progression than conventional PET scans and radiographic response criteria, according to a study published in the Journal of Clinical Oncology by Mark Roschewski, MD, of the National Cancer Institute, and colleagues.
Researchers used data from five prospective studies assessing frontline anthracycline-based chemotherapy in patients with LBCL. They collected ctDNA measurable residual disease (MRD) in 409 plasma specimen from 137 patients (median age, 62 years; 48% had high-intermediate or high International Prognostic Index scores). Most patients (81%) had diffuse LBCL.
Detectable ctDNA rates decreased during therapy; 55% of patients had undetectable ctDNA after two cycles of treatment and 78% at the end of therapy. “The achievement of undetectable MRD was prognostic after [two] cycles and at end of therapy,” the authors noted as to why these timepoints were used.
At a median follow-up of 37 months, two-year progression-free survival (PFS) was 67% for patients with detectable versus 96% with undetectable ctDNA after two treatment cycles (P=0.0025). At the end of therapy, PFS rates were 29% and 97%, respectively (P<0.0001).
Among 96 patients with a negative PET scan at end of therapy, 13 (13.5%) had detectable MRD, and the two-year PFS was 31%.
Most patients (94%) with undetectable ctDNA were alive without disease progression at follow-up compared with 68% who had progressed or died in the detectable ctDNA cohort.
MRD status at the end of treatment was more predictive of treatment failure than conventional lymphoma criteria using PET scans, the authors found.
“Detectable ctDNA identified patients at high risk for relapse regardless of PET scan results, and foreshadowed recurrences up to 18 months later while nearly all patients with undetectable ctDNA maintained remission,” the authors concluded, noting the “critical importance of ultrasensitive analytic thresholds.”
The researchers noted the study is limited by the “practical barriers” to widespread MRD use in LBCL, including turnaround times, available testing, and standardization of collections.
Reference
Kumar SK, Harrison SJ, Cavo M, et al. Remission assessment by circulating tumor DNA in large B-cell lymphoma. J Clin Oncol. 2025:101200JCO2501534. doi:10.1200/JCO-25-01534
