Outpatient Epcoritamab Dosing Feasible in R/R DLBCL, Study Finds

Key Clinical Summary

• Outpatient monitoring after first full dose (FFD) of epcoritamab was feasible in 92% of patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
• Cytokine release syndrome (CRS) occurred in 40.2% of patients, mostly low grade, with no grade ≥3 CRS in outpatient-monitored patients.
• Overall response rate reached 62.0%, with a 42.4% complete response rate in second-line or later treatment.

Epcoritamab, a CD3 × CD20 bispecific antibody, may be safely administered with outpatient monitoring after the first full dose (FFD) in patients with R/R DLBCL, according to findings from the phase 2 EPCORE NHL-6 trial conducted across the US and Puerto Rico.

Outpatient Dosing Shows Manageable Safety

The multicenter EPCORE NHL-6 trial evaluated 92 patients with second-line or later (2L+) DLBCL receiving subcutaneous epcoritamab. Traditionally, bispecific antibodies require 24-hour inpatient monitoring after the first full dose due to risks of CRS and neurotoxicity.

Patients received step-up dosing followed by a 48-mg full dose beginning on cycle 1, day 15. After the FFD, most patients (81 of 88 evaluable) were monitored in the outpatient setting, with instructions to remain within 30 minutes of a hospital and receive CRS prophylaxis.

At a median follow-up of 7.6 months, 50% of patients remained on treatment. CRS occurred in 40.2% of patients, primarily low grade (grade 1-2 in 38.0%), with only 2.2% experiencing grade 3 events. Among outpatient-monitored patients, 24 developed CRS within 1 week, and 13.6% required hospitalization for management.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 7.6% of patients, mostly grade 1-2. All CRS and ICANS events resolved and did not lead to treatment discontinuation.

Efficacy outcomes were notable, with an overall response rate (ORR) of 62.0% and a complete response (CR) rate of 42.4%. Response rates were consistent across treatment lines, with higher CR rates observed in second-line vs later-line settings (47.6% vs. 38.0%).

Outpatient Model Reduces Burden, Expands Access

These findings suggest a shift in care delivery for patients receiving bispecific antibodies in R/R DLBCL. Outpatient monitoring after the first full dose of epcoritamab could reduce the need for routine hospitalization, easing capacity constraints for oncology centers and lowering costs associated with inpatient care.

For managed care stakeholders, the ability to limit hospitalization to reactive cases—rather than mandatory admission—may simplify prior authorization and reimbursement processes. The study reported a median time of 3.1 hours from CRS onset to hospital admission when needed, indicating that outpatient monitoring can still support timely escalation of care.

Additionally, outpatient administration may expand access, particularly for patients treated in community settings or those facing logistical barriers to inpatient care. This approach aligns with broader trends toward decentralizing cancer treatment and optimizing resource utilization.

Investigators Emphasize Safety and Feasibility

Investigators noted that “patients with R/R DLBCL were successfully administered subcutaneous epcoritamab, and nearly all were monitored in the outpatient setting,” with CRS events described as “predictable and consistent” in timing. They emphasized that “CRS and ICANS occurring in patients monitored outpatient were successfully managed and resolved,” supporting the safety of this approach across care settings.

Supports Shift to Outpatient Care

The EPCORE NHL-6 trial demonstrates that outpatient monitoring after epcoritamab initiation is feasible and safe in R/R DLBCL. These findings may support broader adoption of outpatient protocols, improving access while reducing the burden on inpatient oncology resources.

Reference

Andorsky D, Torres 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.