Outpatient Epcoritamab Demonstrates Efficacy and Safety in R/R DLBCL

Updated results from the phase 2 EPCORE NHL-6 clinical trial (NCT05451810) presented at the Society of Hematologic Oncology (SOHO) Annual Meeting indicate that epcoritamab (Epkinly), a subcutaneously administered T-cell–engaging bispecific antibody, can be safely and effectively dosed and monitored in an outpatient setting for adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). These findings support the potential for increased access to this therapeutic option outside of the inpatient hospital setting, which is a significant step toward decentralizing complex oncologic care.¹

Eighty-eight patients received the first full dose of epcoritamab monotherapy at 48 mg, with 81 patients (92%) in the outpatient setting and 7 (8%) in the inpatient setting. In the outpatient population, 57 patients (70%) did not experience cytokine release syndrome (CRS) during the first full dose period. In the overall population, CRS occurred with the first full dose in 21 patients (30%) in the outpatient setting and 3 in inpatient. All events were grade 1 to 2, and 10 (12%) patients were managed in the outpatient setting, while 11 (13.6%) required inpatient care. CRS events resolved with a median time of 2 days, and no events led to treatment discontinuation. Immune cell-associated neurotoxicity syndrome (ICANS) occurred in 7 patients (7.6%) but were primarily grades 1 to 2 and had a median time to resolution of 3 days.

Regarding efficacy, the overall response rate (ORR) was 64.3% with a complete response (CR) rate of 47.6% at a median follow-up of 5.8 months in patients (n = 42) treated with epcoritamab after 1 prior line of systemic therapy. In patients treated with epcoritamab following 2 or more lines of systemic therapy (n = 50), with a median follow-up of 10.8 months, there was an ORR of 60.0% and a CR rate of 38.0%.

“The EPCORE NHL-6 trial results are notable, as current bispecific antibody treatments for relapsed and refractory diffuse large B-cell lymphoma patients may require in-hospital monitoring for cytokine release syndrome after certain initial doses and as needed after subsequent doses,” said Jeff Sharman, MD, Disease Chair, Hematology Research, Sarah Cannon Research Institute (SCRI) at Willamette Valley Cancer Institute in Eugene, Oregon. “The possibility of treating patients in the outpatient setting is encouraging, and it may enable more people to have access to this treatment option across various sites of care, including community settings.”

The successful administration of epcoritamab in an outpatient setting marks a critical advance in the management of R/R DLBCL. By eliminating the need for mandatory hospitalization, this approach can reduce the burden on both patients and the health care system. Patients may experience greater convenience and a higher quality of life by avoiding prolonged inpatient stays. Furthermore, expanding treatment to the outpatient setting could help alleviate the strain on hospital beds and resources, making this effective therapy more broadly accessible.

As a single-agent therapy, epcoritamab has demonstrated deep and durable responses in a patient population with a high degree of disease refractoriness, including those with prior CAR T-cell therapy. The data from the EPCORE NHL-6 trial add to the growing body of evidence supporting the safety and efficacy of this therapeutic class. The high ORR and CR rates, particularly in patients with earlier-stage disease progression, further establish epcoritamab as a promising option for patients who have exhausted traditional lines of therapy.

Future research will likely continue to explore the optimal use of epcoritamab, including its potential in earlier lines of therapy and in combination with other antineoplastic agents. Continued real-world evidence and long-term follow-up data will be essential to fully characterize the long-term safety and durability of responses in the outpatient setting.

Recently, in data published last month, epcoritamab showed benefits in follicular lymphoma, meeting the primary end points of the phase 3 EPCORE FL-1 study (NCT05409066).² Here, epcoritamab led to statistically significant and clinically meaningful improvements when combined with rituximab (Rituxan) and lenalidomide for the treatment of adult patients with relapsed/refractory follicular lymphoma.

FAQs

What is epcoritamab and how does it work?

Epcoritamab is a bispecific antibody designed to target both the CD3 receptor on T cells and the CD20 antigen on B-cell lymphoma cells. By bridging these 2 cell types, it brings the patient's own T cells into close proximity with the cancerous B cells, activating the T cells to destroy the lymphoma cells.

What is the significance of administering epcoritamab in an outpatient setting?

Administering epcoritamab in an outpatient setting allows patients to receive treatment without the need for a prolonged hospital stay. This can significantly improve a patient's quality of life, reduce health care costs, and increase accessibility to the treatment, particularly for those who live far from a specialized cancer center.

What is cytokine release syndrome (CRS) and why is it a concern with treatments like epcoritamab?

CRS is a systemic inflammatory response that can occur when T cells are activated and release a large number of cytokines. Symptoms can range from fever and chills to more severe effects on major organs. It is a common, though often manageable, side effect of T-cell–engaging therapies like epcoritamab.

How do the updated results from the EPCORE NHL-6 trial affect clinical practice?

The updated results suggest that epcoritamab can be safely and effectively administered in an outpatient setting, with manageable toxicities. This information may encourage clinicians to consider this treatment option for eligible R/R DLBCL patients outside of a traditional inpatient hospital setting, potentially leading to more widespread adoption and access.

This article was generated with assistance from Google Gemini. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. Genmab Announces Updated Results from Phase 2 EPCORE® NHL-6 Study Evaluating Epcoritamab Monotherapy in the Outpatient Setting in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). News release. Genmab. September 3, 2025. Accessed September 3, 2025. https://tinyurl.com/5d9s625w

2. Genmab Announces Phase 3 EPCORE® FL-1 Clinical Trial Met Dual Primary Endpoints in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL). News release. Genmab. August 7, 2025. Accessed September 3, 2025. https://tinyurl.com/3jtn38au