Real-World ctDNA Monitoring Shows MRD Clearance Predicts Relapse Risk and Survival Outcomes for DLBCL: HOVON-902 Analysis
Key Clinical Summary
- Population and Design: Prospective real-world HOVON-902 analysis of 150 patients with LBCL (94% DLBCL-NOS, 6% HGBCL; median age 68 y) treated with R-CHOP or DA-EPOCH-R; longitudinal ctDNA (PhasED-Seq) monitoring at 11 timepoints over 2 years and median follow-up 37 months.
- Efficacy and MRD Dynamics: MRD clearance rose progressively (28% at cycle 2 → 81% at end-of-treatment); MRD positivity at any time correlated with inferior 3-year PFS (69% → 11%). Failure to achieve early (≥2-log) or major (≥2.5-log) molecular response predicted significantly worse PFS (HR 3.2; 95% CI, 1.7–5.9; P < .001).
- Clinical Relevance: Serial ctDNA MRD monitoring identified 91% of relapses and achieved 17% higher sensitivity than imaging, confirming its prognostic and predictive value for personalized risk-adapted surveillance and treatment optimization in frontline DLBCL.
Measurable residual disease (MRD) clearance using serial circulating tumor DNA (ctDNA) assessment was predictive of relapse risk and survival among patients with diffuse large B-cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) or dose-adjusted etoposide phosphate, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin, rituximab (DA-EPOCH-R).
These results were presented by Steven Wang, MD, Amsterdam University Medical Center, Amsterdam, Netherlands, at the 2025 ASH Annual Meeting & Exposition.
Researchers conducted a prospective, real-world analysis of patients enrolled in the HOVON-902 study to determine the complete longitudinal dynamics of ctDNA for LBCL. Longitudinal ctDNA monitoring using PhasED-Seq was performed at 11 time points from baseline through 2 years of surveillance.
The study enrolled 150 patients with LBCL with over 1000 plasma samples, of which 94% were DLBCL not otherwise specified (NOS) and 6% had high-grade B-cell lymphoma (HGBCL). The median age was 68 years (range, 19 to 88) and 66% of patients were male. About 80% of patients had advanced-stage disease. The median follow-up was 37 months (range, 1.4 to 55.4), and the 3-year progression-free survival (PFS) rate was 81% and the 3-year overall survival (OS) was 88%.
During first line therapy, MRD clearance increased with each induction cycle, 28% at cycle 2 day 1, 51% at cycle 3 day 1, 64% at cycle 4 day 1, and 81% at the end-of-treatment (EOT). MRD positivity at each timepoint was associated with worse PFS, with the 3-year PFS declining from 69% among patients MRD-positive at cycle 2 day 1 to 11% at EOT.
Patients who failed to achieve early molecular response (EMR), defined as ≥2-log10 decrease in ctDNA, or major molecular response (MMR), defined as ≥2.5-log10 decrease, had significantly inferior 3-year PFS (EMR hazard ratio [HR] 3.2; 95% confidence interval [CI], 1.7 to 5.9; P < .001).
During surveillance, 91% of relapsed patients were MRD-positive at end of therapy or at follow-up, and 99% of non-relapsing patients were MRD-negative by the end of surveillance, suggesting a 17% gain for ctDNA monitoring in clinical sensitivity over current imaging-based strategies.
The researchers concluded, “Our findings confirm the prognostic value of on-treatment MRD and molecular response assessment.”
They added, “Our study provides a comprehensive overview of ultrasensitive MRD detection and how it might inform personalized surveillance and treatment strategies for LBCL.”
Source:
Wang S, Nijland M, Bilgin Y, et al. Longitudinal circulating tumor DNA dynamics during & after first-line therapy in a national cohort of large B-cell lymphomas. Dec 6-9, 2025; Orlando, FL. Abstract: 474
