MRD negativity by ctDNA and PBMCs predicts prolonged survival in relapsed follicular lymphoma
Investigators analyzed minimal residual disease using the clonoSEQ assay on peripheral blood mononuclear cells and circulating tumor DNA in patients with relapsed or refractory follicular lymphoma treated with epcoritamab. Most evaluable patients achieved MRD negativity by cycle 3 day 1, and early MRD-negative status strongly correlated with prolonged progression-free survival regardless of radiographic response. Patients who remained MRD positive despite partial or complete clinical responses experienced significantly shorter progression-free survival compared with MRD-negative counterparts. These findings demonstrate that serial molecular MRD assessment complements conventional imaging and may inform future trial endpoints and clinical decision-making in follicular lymphoma.
The original study
MRD-negativity by PBMCs and ctDNA confirms deep and durable responses following epcoritamab monotherapy in R/R FL.
- Authors
- Altintas I, Morehouse C, Favaro E, Rana A, Karavitis J, Szafer Glusman E, et al.
- Journal
- Blood advances
- Type
- Journal Article
- PMID
- 42431612
Original abstract
In EPCORE® NHL-1 (NCT03625037), the CD3×CD20 bispecific antibody epcoritamab demonstrated promising efficacy and manageable safety in patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy. Using the clonoSEQ® assay, we evaluated minimal residual disease (MRD) status using peripheral blood mononuclear cells (PBMCs) and/or circulating tumor DNA (ctDNA) at prespecified time points and investigated correlation with clinical outcomes. Epcoritamab induced rapid conversion to MRD-negativity, with most MRD-evaluable patients reaching MRD-negativity by cycle (C) 3 day (D) 1 as measured by either analyte. MRD-negativity at C3D1 landmark by either analyte correlated with prolonged progression-free survival (PFS; median not reached) irrespective of radiographic response status. PFS was comparable among patients with overall MRD-negativity by PBMCs or ctDNA, regardless of challenging-to-treat disease features. By C3D1 and C5D1 landmarks, patients with complete or partial response as assessed by positron emission tomography/computed tomography (PET/CT) who were MRD-positive had a shorter PFS compared with those who were MRD-negative. In multivariable analyses at week 12 and week 18 PET/CT landmarks, MRD-negative responders by PBMC assessment (week 12) and by both PBMC and ctDNA assessment (week 18) had significantly improved PFS when adjusted for baseline clinical risk factors. These analyses demonstrate that MRD-negativity is associated with rapid molecular responses to epcoritamab and prolonged PFS in patients with R/R FL, underscoring the value of MRD analysis to complement conventional response assessment. These findings may aid future clinical trial design or clinical practices in FL.