# ctDNA-guided escalation and de-escalation in frontline DLBCL

Source: https://onco.cc/ideas/idea-ctdna-guided-dlbcl-frontline/  
OnCo record `idea-ctdna-guided-dlbcl-frontline` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Use an ultra-sensitive blood test after two cycles to decide who needs more than R-CHOP and who can stop early.

## Summary

The idea is to use an ultra-sensitive ctDNA assay such as PhasED-seq after two cycles of R-CHOP in frontline diffuse large B-cell lymphoma to decide who needs escalation and who can stop early. Interim PET has poor positive predictive value, whereas ctDNA clearance after cycle 2 or at end of treatment predicts cure better, and ctDNA kinetics track outcome across cohorts. The hypothesis is that patients with undetectable ctDNA after two cycles do as well with four cycles as six, while those with detectable ctDNA benefit from switching to a bispecific-containing regimen such as epcoritamab-R-CHOP. The test is a randomised response-adapted trial with ctDNA-defined arms, non-inferior for de-escalation and superior for escalation on event-free survival.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: Patients with undetectable ctDNA after two cycles of R-CHOP have equivalent EFS with 4 versus 6 cycles; patients with detectable ctDNA benefit from switching to a bispecific-containing regimen.
- Rationale: Interim PET has poor positive predictive value; ctDNA kinetics correlate with outcome across cohorts.
- Proposed test: Randomised response-adapted trial with ctDNA-defined arms and EFS non-inferiority (de-escalation) and superiority (escalation) endpoints.
- Maturity: early-clinical

## Sources

- Kurtz et al., Circulating tumour DNA measurements as early outcome predictors in diffuse large B-cell lymphoma (Journal of Clinical Oncology 2018): https://doi.org/10.1200/JCO.2018.78.5246

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/)
- technologies: [ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)](https://onco.cc/technologies/ctdna-lymphoma-monitoring/)
- drugs: [Epcoritamab](https://onco.cc/drugs/epcoritamab/), [Polatuzumab vedotin](https://onco.cc/drugs/polatuzumab-vedotin/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- trials: [A Study of Subcutaneously Injected Epcoritamab Plus Oral Lenalidomide Tablets Compared to Intravenously (IV) Infused Rituximab Plus IV Infused Gemcita](https://onco.cc/trials/nct06508658/), [A Sub-study Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL) in China](https://onco.cc/trials/nct07226752/), [EPCORE DLBCL-1](https://onco.cc/trials/epcore-dlbcl-1/), [EPCORE DLBCL-2](https://onco.cc/trials/epcore-dlbcl-2/), [EPCORE NHL-1](https://onco.cc/trials/epcore-nhl-1/)
- key papers: [Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma](https://onco.cc/key-papers/paper-kurtz-j-clin-oncol/), [Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial](https://onco.cc/key-papers/paper-epcoritamab-dlbcl-blood-2025/), [Epcoritamab: First Approval](https://onco.cc/key-papers/paper-epcoritamab-dlbcl-drugs-2023/)

---
JSON: https://onco.cc/api/v1/entities/idea-ctdna-guided-dlbcl-frontline.json