TOPLINE

In an exploratory analysis, epcoritamab was associated with a rapid shift to minimal residual disease (MRD) negativity in patients with relapsed or refractory (R/R) follicular lymphoma, and most patients achieved MRD negativity by cycle 3, day 1, as measured using peripheral blood mononuclear cells (PBMCs) or circulating tumor DNA (ctDNA). MRD negativity at that timepoint was associated with longer progression-free survival (PFS). Overall MRD negativity was also linked to longer PFS in high-risk subgroups, including patients with four or more prior treatment lines, double-refractory disease, or high Follicular Lymphoma International Prognostic Index scores.

METHODOLOGY

• Follicular lymphoma often relapses, and outcomes worsen with each successive treatment line. In the ongoing phase 1/2 EPCORE NHL-1 trial, epcoritamab, a bispecific antibody, produced deep, durable responses in heavily pretreated patients with R/R follicular lymphoma. MRD testing, which detects tiny amounts of residual cancer, may help predict response durability, but blood-based methods remain exploratory.
• Researchers conducted an exploratory analysis of the phase 1/2 EPCORE NHL-1 trial, which enrolled 128 adults with CD20-positive follicular lymphoma (grade 1-3A) who had received two or more prior treatment lines and had disease that was refractory to their last therapy. They assessed MRD status using the clonoSEQ assay in PBMCs (96 MRD-evaluable patients) and ctDNA (105 MRD-evaluable patients). 
• Patients received subcutaneous epcoritamab 48 mg once weekly in cycles 1-3, every 2 weeks in cycles 4-9, and every 4 weeks from cycle 10 onward until progressive disease or unacceptable toxicity.
• MRD samples were collected before dosing on day 1 of cycles 1, 3, 5, 7, 10, and 13 and on day 22 of cycle 1; radiographic disease evaluation by PET-CT occurred every 6 weeks for the first 24 weeks, every 12 weeks through week 48, and every 6 months subsequently.
• The primary outcome of the trial was overall response; MRD negativity and its association with PFS were assessed at prespecified landmarks (cycle 1, day 22; cycle 3, day 1; and cycle 5, day 1).

TAKEAWAY

• Among MRD-evaluable patients, 64 of 96 (66.7%) achieved overall MRD negativity by PBMC assessment and 72 of 105 (68.6%) by ctDNA assessment. Of the patients who attained MRD negativity, most did so by cycle 1, day 22, or cycle 3, day 1 (90.6% of patients assessed using PBMCs and 83.3% of patients assessed using ctDNA). 
• Concordance in overall MRD status at the patient level between PBMC and ctDNA assessments was high, with 85 of 94 patients (90.4%) with matched samples showing concordant results.
• In landmark analyses, MRD negativity was associated with longer PFS at day 22 of cycle 1, with a stronger association for PBMC testing (P = .0007) than for ctDNA testing (P = .0372). The association was even stronger at day 1 of cycle 3, with patients with MRD negativity having significantly longer PFS than patients with MRD positivity by both assessment methods (P < .0001 for each). Overall MRD negativity was also linked to longer PFS in high-risk subgroups, including patients who received four or more prior treatment lines, double-refractory disease, or high Follicular Lymphoma International Prognostic Index scores.
• Among patients with complete or partial response on PET/CT, patients with MRD positivity had shorter PFS than those with MRD negativity. At the week 12 landmark, the difference was significant with PBMC testing (P < .0001) but not with ctDNA testing (P = .1588). At the week 18 landmark, the difference was significant with both methods (P = .0002 with the PBMC assessment and P = .0003 with the ctDNA assessment).
• This association persisted in multivariable analyses of responders. MRD positivity by PBMC testing independently predicted worse PFS at both timepoints (week 12: hazard ratio [HR], 6.50; P = .0065; week 18: HR, 9.18; P = .0037). MRD positivity by ctDNA testing predicted worse PFS at week 18 (HR, 11.92; P = .0173).

IN PRACTICE

"These findings underscore the potential future value of MRD assessment as a complementary tool to radiographic imaging for monitoring treatment response and guiding response-adaptive treatment strategies,″ the authors wrote, adding that ″the findings suggest that both PBMC and ctDNA analytes have a role in MRD assessment for R/R FL [follicular lymphoma], and the optimal timing for prognostic evaluation is highly dependent on the specific analyte and the analytical approach used."

SOURCE

The study, led by Işıl Altıntaş, Genmab in Utrecht, Netherlands, was published online in Blood Advances.

LIMITATIONS

The analysis was exploratory, and the MRD assay was not approved for clinical use in follicular lymphoma at the time of publication. Samples that were missing at the landmark timepoints may have caused the time to first MRD negativity to be underestimated and may have reduced the apparent differences in PFS among groups in the landmark analyses. MRD testing was more frequent in this trial than is feasible in routine practice because of cost and turnaround time.

DISCLOSURES

The study was supported by Genmab A/S and AbbVie. Ten authors reported being employees of and owning stock/shares in Genmab. Two authors declared being employees of and owning stocks/shares in AbbVie. Several authors reported consulting fees, research funding, honoraria, or advisory board roles from various pharmaceutical companies, including AbbVie, Genmab, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, and others. Full author disclosures are reported 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.