Clinical implications of circulating tumor DNA in predicting the outcome of diffuse large B cell lymphoma patients receiving first-line therapy
Miaomiao Li, Lan Mi, Chunyang Wang, Xiaojuan Wang, Jianhua Zhu, Jianhua Zhu et al. · 2022 · 35 citationsRead the paper
BACKGROUND: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored. METHODS: Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients. RESULTS: The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission). CONCLUSIONS: CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.
What the full text shows
Shown in the lab- Pretreatment ctDNA level is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS). — PFS adjusted HR 2.47; OS adjusted HR 2.49 (Chinese DLBCL patients)
- Molecular responders (those with a larger decrease in ctDNA after two treatment cycles) have significantly better survival outcomes. — PFS: unreached vs 6.25 months (HR 5.348); OS: unreached vs 25.87 months (HR 4.0) (After initial two treatment cycles)
- Interim ctDNA clearance (after four cycles) is an independent prognostic marker comparable to interim PET-CT for PFS. — PFS HR 3.65; OS HR 3.536 (Patients with paired baseline tumor or plasma samples)
- Posttreatment ctDNA detection of minimal residual disease (MRD) predicts recurrence in patients with radiographic complete remission (CR). — RFS HR 6.471 (Patients who reached radiographic CR)
- Pretreatment plasma ctDNA shows high sensitivity in detecting variants verified in tumor specimens. — 77.9% sensitivity (22 paired baseline tumor/plasma samples)
- KLHL14 mutations are associated with achieving complete remission (CR). — 25% in CR group vs 0% in non-CR group (p=0.015) (Pretreatment plasma samples)
- Setup
- 73 Chinese DLBCL patients; 43 primary tumor specimens and 162 serial blood samples.
- How
- Targeted next-generation sequencing (NGS) using a lymphoma-specific panel (188 genes) was performed on plasma cfDNA and tumor gDNA. Longitudinal ctDNA levels were calculated as haploid genome equivalents (hGE/mL) and correlated with clinical outcomes using Cox proportional hazards models.
- Limitations
- Retrospective study design · Small sample size for certain subgroups (e.g., KLHL14 analysis) · Limited to a specific Chinese cohort
Summarized by Gemma 4 from the open-access full text · 8 Oct 2026. Read it