TOPLINE

Minimal residual disease (MRD) negativity assessed through peripheral blood mononuclear cells (PBMCs) and circulating tumor DNA (ctDNA) correlated with prolonged progression-free survival in patients with relapsed or refractory follicular lymphoma treated with epcoritamab. Most MRD-evaluable patients achieved MRD negativity by cycle 3 day 1, with median progression-free survival not reached among MRD-negative patients regardless of challenging disease features.

METHODOLOGY

• Some patients with follicular lymphoma achieve long-term remission after first-line therapy, whereas many experience relapse or develop resistance characterized by declining response rates and progressively shorter intervals between treatments. This exploratory study provided MRD analysis in patients with relapsed or refractory follicular lymphoma receiving bispecific antibody therapy using the same assay for direct comparison of PBMCs and ctDNA.
• Researchers evaluated MRD status using the clonoSEQ assay in 128 adults with CD20-positive, histologically confirmed grade 1-3A follicular lymphoma who had received at least two prior lines of therapy and were relapsed or refractory to their last treatment in the phase 1/2 EPCORE NHL-1 trial conducted in the US and internationally.
• Participants received subcutaneous epcoritamab 48 mg in 28-day cycles with a two-step priming regimen (0.16 mg on day 1 and 0.8 mg on day 8 in cycle 1) administered once weekly in cycles 1-3, every 2 weeks in cycles 4-9, and every 4 weeks from cycle 10 until progressive disease or unacceptable toxicity.
• MRD assessment was performed on PBMCs and ctDNA samples collected at prespecified timepoints (cycles 1, 3, 5, 7, 10, and 13) to detect clonally rearranged immunoglobulin loci, with the MRD-evaluable population consisting of 96 patients for PBMC analysis and 105 patients for ctDNA analysis.
• Radiographic disease evaluation by PET-CT was performed every 6 weeks for the first 24 weeks, then every 12 weeks through 48 weeks, and every 6 months thereafter, with response assessed by an independent review committee.
• Analysis included landmark progression-free survival assessments at cycle 1 day 22, cycle 3 day 1, and cycle 5 day 1, as well as multivariable Cox regression models at week 12 and week 18 PET-CT landmarks adjusting for baseline clinical risk factors including Follicular Lymphoma International Prognostic Index score, time since last treatment, and number of prior lines of therapy.

TAKEAWAY

• MRD negativity at cycle 3 day 1 by either PBMC or ctDNA assessment correlated with significantly prolonged progression-free survival compared with MRD positivity (PBMCs: P < .0001; ctDNA: P < .0001), with median progression-free survival not reached in MRD-negative patients.
• Overall, MRD negativity was achieved in 66.7% of patients by PBMC analysis and 68.6% by ctDNA analysis, with comparable progression-free survival outcomes regardless of challenging disease features such as progression within 24 months and double-refractory status.
• In multivariable analysis at week 12, MRD status by PBMC assessment was an independent predictor of progression-free survival (hazard ratio [HR], 6.50; P = .0065), and at week 18, both PBMC (HR, 9.18; P = .0037) and ctDNA (HR, 11.92; P = .0173) assessments independently predicted progression-free survival when adjusted for baseline clinical risk factors.
• Among patients achieving complete or partial response by PET-CT at week 12 and week 18 landmarks, those who were MRD positive had significantly shorter progression-free survival than those who were MRD negative (week 12 PBMCs: P < .0001; week 18 PBMCs: P = .0002; week 18 ctDNA: P = .0003).

IN PRACTICE

“MRD-negativity is associated with rapid molecular responses to epcoritamab and prolonged [progression-free survival] in patients with [relapsed or refractory follicular lymphoma], underscoring the value of MRD analysis to complement conventional response assessment. These findings may aid future clinical trial design or clinical practices in [follicular lymphoma],” authors of the study wrote.

SOURCE

The study was led by Isil Altintas of Genmab in Utrecht, Netherlands, and Christopher Morehouse, David Soong, and Andrew J. Steele of Genmab in Plainsboro, New Jersey. It was published online in Blood Advances.

LIMITATIONS

The MRD assay used (clonoSEQ) was not approved for clinical use in follicular lymphoma at the time of publication, underscoring the need for improved sensitivity and technical standardization to minimize false or inconclusive results. Potential unavailability of samples at landmark timepoints may lead to underestimation of time to first MRD negativity and differences among groups in landmark progression-free survival assessments. The misalignment of MRD and PET-CT timing resulted in exclusion of patients from certain analyses, affecting sample size and statistical outcomes. According to the authors, MRD assessment in clinical practice cannot be performed as frequently as in this first-in-human trial due to cost and assay turnaround time. Small patient numbers in stratified analyses, particularly when comparing complete response patients with partial response patients by MRD status, precluded statistically meaningful comparisons between groups.

DISCLOSURES

This study received funding from Genmab A/S and AbbVie. Altintas, Morehouse, Elena Favaro, Ali Rana, John Karavitis, Tahamtan Ahmadi, Mark Fereshteh, Maria Jure-Kunkel, Soong, and Steele disclosed employment with and stock ownership in Genmab. Edith Szafer-Glusman and Kevin Zhao disclosed employment with and stock ownership in AbbVie. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.