Reference: January 2026 | Issue 1 | Vol 12 | Page 46
In November 2025, the US Food and Drug Administration (FDA) approved epcoritamab with rituximab and lenalidomide for relapsed or refractory (R/R) follicular lymphoma. At the ASH Annual Meeting in December, attendees were able to review the data that supported the approval.
In the trial, patients with follicular lymphoma had a significantly higher response to treatment and a nearly 80 per cent reduction in the risk of death or disease progression with epcoritamab in addition to the standard second-line regimen versus the standard regimen alone.
The study is the first reported randomised controlled trial to test a bispecific antibody combination in follicular lymphoma and suggests the combination could offer an effective alternative to chemotherapy that can be safely administered on an outpatient basis.
The study randomised 488 patients with R/R follicular lymphoma to receive epcoritamab plus rituximab and lenalidomide (R2) or R2 alone for up to 12 cycles. At a median follow-up of just under 15 months, the group receiving epcoritamab plus R2 showed an overall response rate (ORR) of 95.1 per cent versus 79.2 per cent in the control group. Progression-free survival (PFS) was 85.5 per cent versus 40.2 per cent at 16 months.
Almost 83 per cent of patients in the epcoritamab plus R2 arm had a complete response (CR) to treatment versus 49.8 per cent among those who received R2 alone. Participants who received epcoritamab plus R2 also showed a significantly longer duration of response and CR. The results were consistent across all subgroups.
At 16 months, 92.8 per cent of patients in the epcoritamab group remained free from new anti-lymphoma treatments, compared with 64.9 per cent among those who received R2 alone.
“The addition of epcoritamab to rituximab and lenalidomide very substantially increased the response rates, depth of response, and duration of benefit and, therefore, may represent a new standard of care in patients with follicular lymphoma,” said lead study author Lorenzo Falchi, assistant attending physician in the lymphoma service, Memorial Sloan Kettering Cancer Centre, New York.
“We are at a point in time when chemo-free approaches based on immunotherapy can seriously challenge chemotherapy as the standard of care. We will not know for a long time if [this regimen] is curative, but it’s certainly the beginning of a bright era for chemo-free therapy for follicular lymphoma.”
Participants who received epcoritamab plus R2 experienced a higher rate of adverse events, with grade 3 or 4 treatment-related adverse events occurring in 90.1 per cent of patients receiving epcoritamab and 67.6 per cent of patients in the control group. This increase was driven largely by a higher rate of neutropenia and infections among those receiving epcoritamab. There was no evidence of neurological toxicity and no reports of grade 3 or 4 cytokine release syndrome (CRS).
“There has been some hesitancy to use bispecific antibodies in a community setting because of CRS,” said Dr Falchi. “The prospect of a subcutaneous, completely outpatient treatment that does not result in a significant rate of CRS is good news for giving more patients the best opportunity for a response.”
The study also tested two different step-up dosing regimens for the epcoritamab-R2 combination, showing that three initial smaller doses resulted in a reduced rate of low-grade CRS compared with a course of just two initial smaller doses.
A separate study is underway to test the epcoritamab-R2 combination in a frontline setting. Dr Falchi added that epcoritamab could also be investigated as a single-agent treatment for patients who are not candidates for R2.
