Results Support Giving Epcoritamab in Outpatient Setting for DLBCL

The big question in administration of bispecific antibodies these days is how quickly they can move to the outpatient setting—making them more convenient and cost-effective. Now, new study results for a successful bispecific therapy may take outpatient treatment a step further.¹

Epcoritamab (Epkinly; Genmab/AbbVie), a subcutaneous CD3 × CD20 bispecific T-cell–engaging antibody, is approved as a monotherapy for patients previously treated with at least 2 therapies for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Epcoritamab is also approved in combination with lenalidomide and rituximab for second-line treatment of FL.

Right now, the FDA requires that patients with DLBCL receiving the first full 48-mg dose be monitored inpatient for 24 hours, as clinicians check for signs of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS).² This protocol, based on the pivotal EPCORE-NHL-1 trial (NCT03625037) that led to approval, can limit access for some patients, particularly at community practices.

The phase 2 EPCORE NHL-6 trial (NCT05451810) was designed to determine whether this monitoring requirement could be safely shifted to the outpatient setting. Interim results, recently published in Clinical Lymphoma, Myeloma and Leukemia, suggest the inpatient stay can be eliminated for most patients.¹

“Outpatient administration may remove barriers for some patients by facilitating treatment in more localized community-based clinics while reducing costs and caregiver demands,” the authors wrote.

Investigators, led by David Andorsky, MD, of Sarah Cannon Research Institute at Rocky Mountain Cancer Centers in Boulder, Colorado, included physicians from leading community practices; experts say these centers must be the backbone of bispecific distribution channels if there is hope to reach all patients who need these therapies in the future.

Study Design and Patient Population

Patients with relapsed/refractory (R/R) DLBCL who had received at least 1 prior line of therapy, including an anti-CD20 monoclonal antibody, were enrolled across both academic and community sites in the US and Puerto Rico. Epcoritamab was administered subcutaneously in 28-day cycles using a step-up dosing strategy: a 0.16-mg priming dose on cycle 1 day 1, a 0.8-mg intermediate dose on day 8, and then full 48-mg doses beginning day 15, with mandatory CRS prophylaxis throughout cycle 1.

Unless the investigator deemed hospitalization appropriate, patients received the first full dose in the outpatient setting. Patients were required to remain within 30 minutes of the treatment facility for 24 hours and to return the following day for a safety visit.¹

Notably Diverse Enrollment

A notable feature of EPCORE NHL-6 is its diverse enrollment, which is considerably more reflective of the US population than is typical of pivotal oncology trials. Of the 92 patients enrolled, 15.2% identified as Black or African American and 21.7% as Hispanic or Latino, representation that stands in meaningful contrast to the predominantly White populations that have historically dominated clinical trial enrollment.

The median age was 69 years, with one-third of patients aged 75 or older, reflecting a realistic elderly population that commonly bears the burden of DLBCL. Patients were enrolled across both academic (n = 51) and community (n = 41) sites, further broadening the generalizability of findings. Nearly half (45.7%) had second-line disease, while 54.3% were in the third-line or later setting; 23.9% had previously received chimeric antigen receptor T-cell therapy.¹

Safety Data Show Outpatient Dosing Is Feasible

Of the 88 patients who received the first full dose, 81 (92%) did so and initiated monitoring in the outpatient setting. Among these outpatient-monitored patients, 24 (29.6%) developed CRS during the first full dosing period. Critically, no CRS events of grade 3 or higher occurred in outpatients. The overall CRS hospitalization rate among outpatient-dosed patients was 13.6% (11/81), meaning the majority were managed without admission. For those patients who did require hospitalization, the median time from CRS onset to hospital admission was approximately 3 hours; thus, when hospitalization was required, patients were able to gain admission quickly.

Overall, CRS occurred in 40.2% of patients (grade 1, 21.7%; grade 2, 16.3%; grade 3, 2.2%); this distribution was consistent with findings from EPCORE NHL-1.³ ICANS occurred in 7.6% of patients (grade 3 in 1.1%), and all CRS and ICANS events completely resolved. No CRS or ICANS event led to treatment discontinuation.¹

Efficacy Data Align With Earlier Results

Efficacy results were consistent with prior data. The overall response rate (ORR) was 62.0%, and the complete response (CR) rate was 42.4%; responses held up across both second-line (ORR, 64.3%; CR, 47.6%) and third-line or later (ORR, 60.0%; CR, 38.0%) populations. The median time to response was 1.4 months (range, 0.9-4.2) and to CR was 2.7 months (range, 1.2-5.7).

In the overall population, median progression-free survival (PFS) was 5.7 months (range, 4.0-6.4). By line of treatment, median PFS was not reached (NR) with 5.5 months (range, 8.3-NR) of median follow-up in the second-line setting and 4.2 months (range, 1.8-6.4) with 8.1 months of median follow-up in the third-line or later setting.

Thus far, EPCORE NHL-6 data show that outpatient administration and monitoring of epcoritamab is feasible, safe, and effective in R/R DLBCL, investigators have found.

The bispecific “was generally well-tolerated with a manageable safety profile among patients receiving their first full dose in the outpatient setting, indicating outpatient administration of the first full dose is feasible,” the authors wrote. “The feasibility of outpatient administration of epcoritamab underscores its flexibility and represents an important advancement in ensuring patient access across diverse care settings, including community-based centers.”

References

1. Andorsky D, Lopez A, Vaidya R, et al. Epcoritamab monotherapy as outpatient treatment for patients with relapsed/refractory diffuse large B-cell lymphoma: interim results from EPCORE NHL-6. Clin Lymphoma Myeloma Leuk. 2026;S2152-2650(26)00042-X. doi:10.1016/j.clml.2026.02.006
2. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. News release. FDA. May 19, 2023. Accessed March 27, 2026. fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
3. Linton K, Vitolo U, Jurczak W et al. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol. 2024;11(8):e593-e605. doi: 0.1016/S2352-3026(24)00166-2