Early clearance of circulating tumor DNA (ctDNA) could potentially serve as a biomarker for patients with diffuse large B-cell lymphoma (DLBCL) receiving first-line therapy, according to a recently published study in the journal Blood.

Although the introduction of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy has significantly improved prognosis in patients with DLBCL, approximately 30% of patients are treatment-resistant or relapse. 

Currently, the prognosis of patients resistant to first-line therapy is poor. Thus, there is a high interest in assessing biomarkers with the capacity to detect patients unlikely to respond to R-CHOP chemotherapy.

Read more about DLBCL prognosis

ctDNA has successfully been used as a biomarker in a variety of solid and hematological tumors. Several studies have investigated its utility in patients receiving treatment for DLBCL; however, its use as a prognostic factor remains controversial.

Therefore, the authors aimed to assess the correlation between ctDNA clearance and clinical improvement in patients with DLBCL receiving R-CHOP immunochemotherapy. 

The retrospective study included 37 patients whose blood samples were collected before the beginning of treatment (C0) and after 2 treatment cycles (C2). Tumor genomic DNA and cell-free DNA were collected in all patients to detect basal mutations.

In all 37 patients, at least one basal mutation was detected in C0. C2 sampling revealed that the mutation detected in C0 had been cleared in 25 patients. The remission rate of the 25 patients with fast ctDNA clearance was approximately 40% higher than that of patients in the low ctDNA clearance group. Furthermore, the median overall survival of patients in the high ctDNA group was 18 months longer. 

The authors noted that the groups had no significant difference in the baseline characteristics, such as the presence of B symptoms, tumor staging, International Prognostic Index, or lactate dehydrogenase.

“Integrating ctDNA profiling into clinical disease management may help to identify patients at high risk and contribute to individualized treatment,” the authors concluded.

Reference

Song Y, Li M, Mi L, et al. Circulating tumor DNA clearance during treatment as a predictive and prognostic biomarker for diffuse large B-cell lymphoma patients receiving first-line therapy. Blood. Published online November 15, 2022. doi:10.1182/blood-2022-166170