TOPLINE

More than half of the frail older adults with newly diagnosed anthracycline-ineligible diffuse large B-cell lymphoma (DLBCL) who received fixed-duration epcoritamab monotherapy achieved a complete response in a phase 2 trial.

METHODOLOGY

• Older adults with DLBCL often cannot tolerate standard anthracycline-based therapy because of frailty, comorbidities, and limited organ reserve. Existing anthracycline-free options have shown limited efficacy, creating a need for better first-line therapy.
• Epcoritamab is a bispecific antibody approved for treating relapsed or refractory disease. To evaluate the efficacy and safety of fixed-duration epcoritamab monotherapy vs epcoritamab with lenalidomide in the first-line setting, researchers conducted an open-label, multicenter phase 2 randomized selection trial of 111 patients with newly diagnosed CD20-positive LBCL who were ineligible for anthracycline-based chemoimmunotherapy.
• Overall, 108 patients (median age, 83 years; 53% women) received treatment across two stages. In stage one, 88 participants were randomly assigned 1:1 to receive epcoritamab monotherapy (n = 44) or epcoritamab with lenalidomide (n = 44). In both groups, epcoritamab was administered subcutaneously using a two step-up dosing schedule for up to 12 cycles. Lenalidomide was given orally for up to 12 cycles in the combination group.
• The primary endpoint was achieving investigator-assessed complete response according to the Lugano criteria; secondary endpoints included the achievement of overall response, progression-free survival, overall survival, and minimal residual disease (MRD) negativity.

TAKEAWAY

• In stage one, the complete response rate was 63.6% in the epcoritamab monotherapy group with 45.5% in the epcoritamab with lenalidomide group, which led investigators to select monotherapy for stage two expansion (n = 22). Among 66 patients who received epcoritamab monotherapy across stages one (n = 44) and two (n = 22), the complete response rate was 57.6%, overall response rate was 66.7%, and median time to complete response was 2.2 months.
• The median progression-free survival was 13.0 months, with an estimated 12-month progression-free survival of 50.1%; the median overall survival was not reached, with an estimated 12-month overall survival of 66.3%.
• Among 36 evaluable patients receiving monotherapy, 92% achieved MRD negativity at any timepoint after baseline, with 83% of patients with a complete response reaching MRD negativity at cycle three day 1, and most maintained MRD negativity through cycle 12 day 1 and during follow-up.
• The most common treatment-emergent adverse events were infections (68%), fatigue (23%), neutropenia (12%), and hypertension (11%). Serious adverse events occurred in 70% of patients. Cytokine release syndrome was frequent but mostly low grade and resolved rapidly. Two treatment-emergent deaths occurred in stage two.

IN PRACTICE

“Epcoritamab monotherapy shows potential as a chemotherapy-free, fixed-duration treatment option that can reach clinically meaningful responses and durable disease control in older adults with newly diagnosed LBCL,” the authors wrote. “Our findings support the continued development of epcoritamab as a first-line option for frail patients with a long-standing unmet treatment need.”

SOURCE

The study, led by Umberto Vitolo, MD, Candiolo Cancer Institute in Turin, Italy, was published online in Lancet Haematology.

LIMITATIONS

The trial was not powered to compare monotherapy with combination therapy. Anthracycline ineligibility was based on investigator judgment rather than a standardized frailty measure. The trial had a modest sample size, especially in stage two. Follow-up for progression-free survival and overall survival remained immature at analysis. Additionally, the noncomparative stage two design did not allow a direct comparison of benefit with other treatment regimens.

DISCLOSURES

This study was funded by Genmab and AbbVie. Vitolo disclosed receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, Genmab, Gilead, Incyte, MSD, Regeneron, and Sobi, and participation on data safety monitoring boards or advisory boards for AbbVie, Genmab, Gilead, Incyte, MSD, Regeneron, Seattle Genetics, and Sobi. Three other authors reported having employment with Genmab and two of them held stock ownership in Genmab. One author reported having employment with and stock ownership in AbbVie. Full 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.