Epcoritamab Study Points to Safer Outpatient Use in Relapsed/Refractory DLBCL

At the 2025 Society of Hematologic Oncology (SOHO) Annual Meeting, new data from AbbVie's Phase 2 EPCORE® NHL-6 trial offered a compelling update on the potential outpatient administration of epcoritamab, a bispecific T-cell engaging antibody for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). The findings suggest a shift in how—and where—this treatment might be safely administered, with meaningful implications for access and patient experience.

DLBCL remains the most common subtype of non-Hodgkin’s lymphoma, representing roughly a quarter of all NHL cases. While some patients achieve durable remission, a significant portion relapse or develop resistance to frontline therapy. For these individuals, particularly those who have exhausted multiple lines of systemic treatment, therapeutic options can be limited and logistically burdensome—especially when therapies require inpatient administration due to safety concerns like cytokine release syndrome (CRS) or immune cell-associated neurotoxicity syndrome (ICANS).

Epcoritamab, developed in partnership between AbbVie and Genmab, is a subcutaneously administered bispecific antibody designed to bring T cells into close proximity with CD20-expressing B cells, triggering immune-mediated cell death. This mechanism has demonstrated efficacy in B-cell malignancies, but like many bispecifics, it carries a risk of CRS and neurotoxicity—events that often require hospital admission for monitoring, especially during initial dosing.

The EPCORE NHL-6 trial, however, offers early evidence that this paradigm might change. Of the 88 patients who received the first full 48 mg dose of epcoritamab, 92% were monitored in outpatient settings. The majority of adverse events—CRS in 40% of patients and ICANS in 7.6%—were mild (Grade 1 or 2), resolved within days, and did not lead to treatment discontinuation. Importantly, there were no treatment-related fatalities or high-grade toxicities during the initial dosing period, the most critical window for adverse immune responses.

This safety profile opens the door to broader administration in non-hospital settings, which could significantly expand access—particularly in community oncology practices that may not be equipped for inpatient infusions. For patients, outpatient treatment means fewer disruptions, lower costs, and less travel—especially critical for older individuals, who make up the majority of DLBCL diagnoses.

While safety is paramount, efficacy remains the deciding factor. The trial stratified patients by number of prior systemic therapies. Among those who had received only one prior line of treatment, the overall response rate (ORR) was 64.3%, with a complete response (CR) rate of 47.6%. Those with two or more prior therapies showed an ORR of 60.0% and a CR rate of 38.0%. Though preliminary, these results indicate that epcoritamab retains its clinical punch even earlier in the treatment sequence—a key point as studies begin exploring its use beyond the current indication, which is limited to patients who have failed at least two lines of therapy.

Another layer of relevance is the trial’s patient population. Nearly a quarter had received prior CAR T-cell therapy, 83% had advanced-stage disease (Ann Arbor stage III or IV), and over half had high-risk disease based on International Prognostic Index (IPI) scores. In other words, this wasn’t a low-risk cohort, and yet the therapy remained tolerable and effective—reinforcing its potential role in more challenging patient scenarios.

The design of epcoritamab itself is also noteworthy. Using Genmab’s proprietary DuoBody® platform, the drug binds both CD3 on T cells and CD20 on B cells, initiating cytotoxicity in a targeted, controlled fashion. Unlike CAR T-cell therapy, which requires cell harvesting and genetic modification, epcoritamab is off-the-shelf and subcutaneous—offering speed and simplicity that could be transformative in urgent care settings.

Epcoritamab is currently being investigated across five Phase 3 studies evaluating its use in combination with established regimens like R-CHOP and lenalidomide in both newly diagnosed and previously treated patients with DLBCL and follicular lymphoma. As these trials progress, the EPCORE NHL-6 study provides a real-world anchor for what a safer, more accessible rollout of bispecifics might look like.

Regulatory bodies have not yet approved epcoritamab for outpatient use or as a second-line monotherapy. But this latest dataset could move the conversation forward—potentially redefining standards of care not just by who receives treatment, but by where and how it’s delivered. For patients and providers navigating the uncertainties of relapsed DLBCL, that shift could be more than a matter of convenience—it could mean the difference between access and abandonment.

As bispecifics edge closer to outpatient viability, epcoritamab may be setting a precedent: effective immunotherapy doesn’t always have to come with a hospital bed.