MRD negativity by PBMCs and ctDNA confirms deep and durable responses after epcoritamab monotherapy in R/R FL

Abstract In EPCORE NHL-1, 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 their correlation with clinical outcomes. Epcoritamab induced rapid conversion to MRD negativity, with most MRD-evaluable patients reaching MRD negativity by cycle 3 (C3) day 1 (D1) 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 practice in FL. This trial was registered at www.clinicaltrials.gov as NCT03625037.