ideasIdea
ctDNA-guided escalation and de-escalation in frontline DLBCL
Use an ultra-sensitive blood test after two cycles to decide who needs more than R-CHOP and who can stop early.
PhasED-seq ctDNA clearance after cycle 2 or at end of treatment predicts cure better than PET. Frontline regimens now differ (Pola-R-CHP, tafa-len-R-CHOP, epcoritamab-R-CHOP) and could be assigned by early molecular response.
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.
What would test it
Randomised response-adapted trial with ctDNA-defined arms and EFS non-inferiority (de-escalation) and superiority (escalation) endpoints.
Maturity
early clinical