Label Change Helps Remove Barriers to Broader Use of Epcoritamab in DLBCL, Sharman Says

The FDA’s decision to allow outpatient administration of the first full dose of epcoritamab (Epkinly; AbbVie/Genmab) for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) will increase access to the bispecific antibody, according to a leading physician who studied its use in this setting.

Previously, for patients with DLBCL or high-grade B-cell lymphoma, physicians were advised to admit patients receiving the 48-mg dose on day 15 of cycle 1. A label change announced April 1, 2026, calls for physicians to assess whether hospitalization or outpatient monitoring is appropriate” after patients receive the therapy, which is given by subcutaneous injection.¹

The label change came April 1, 2026, just a few days after data from the EPCORE NHL-6 study (NCT05451810) showed that this first full dose could be safely administered in the outpatient setting with proper monitoring in most cases. Interim results from the study were published in Clinical Lymphoma, Myeloma & Leukemia.²

In an interview with The American Journal of Managed Care (AJMC), Jeff Sharman, MD, director of research at the Willamette Valley Cancer Institute and senior author of the study, said that without the FDA label change, scaling delivery of epcoritamab to all eligible patients with DLBCL would be a challenge. “Absent these changes, there remain barriers,” he said. “There are systems in place to administer the medication, but they may be stymied by the need for inpatient hospitalization or access to hospital formularies that don't cover the medication.

“So, there are a lot of barriers, and this…helps remove a number of those barriers, therefore enabling the broader use of the medication,” said Sharman, who is also medical director of hematology research for The US Oncology Network.

How to scale the delivery of bispecifics in blood cancers has been an important topic of conversation in managed care over the past year, especially since the American Society of Hematology Annual Meeting and Exposition in December 2025. There, dozens of abstracts offered evidence that bispecifics will be moving into earlier lines of care, not only in lymphoma but also in multiple myeloma, raising questions of how health systems would meet demand and whether community oncology practices would be ready to manage these patients who require monitoring for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).³ At present, epcoritamab, a CD3 × CD20 bispecific T-cell–engaging antibody, is approved as a monotherapy for patients previously treated with at least 2 therapies for DLBCL and follicular lymphoma (FL). Epcoritamab is also approved in combination with lenalidomide and rituximab for second-line treatment of FL.

According to Blood Cancer United, DLBCL accounts for 25% to 30% of cases of non-Hodgkin lymphoma globally, with approximately more than 25,000 new cases diagnosed in the US annually.⁴

In the interview, Sharman explained that there are compelling reasons for community oncology to administer these therapies in the outpatient setting, for both financial and quality-of-life reasons.

“With bispecific antibodies, of course, there is always some risk of [adverse] effects,” he said. “As we've gained more experience with them, we've become more familiar with how to safely administer these medications in the outpatient setting. That's a big deal for practices, because oftentimes these medications are not on hospital formulary. They're not reimbursed, so it creates access barriers for patients.”

If the first full dose of epcoritamab could be safely administered on an outpatient basis, that’s preferable to a hospital stay, Sharman said. Patients have to go through prior authorization, and there’s some risk of bills being denied, “to think nothing about spending a night in a hospital, typically getting woken up for vital signs and so forth.

“Those are major barriers for patients to receive therapy,” he said.

The label sends a signal to physicians that outpatient administration is in line with standards of care—that it’s perfectly safe and that physicians who offer this route will not face liability. “That really expands the number of physicians capable of administering this. Patients, therefore, are able to receive what's really an important and effective therapy,” Sharman said.

Methods. EPCORE NHL-6 examined outpatient administration and monitoring of epcoritamab after the first full dose in patients who had received at least 2 other treatments for DLBCL. Patients received epcoritamab in 28-day cycles, starting with step-up doses of 0.16 mg and 0.8 mg in cycle 1, followed by the 48-mg full dose starting on day 15. Primary end points were CRS of grade 3 or higher, ICANS, and neurologic events. Patients remained within 30 minutes of the hospital following treatment and received mandatory CRS prophylaxis during the first cycle.²

Results. The study enrolled 92 patients at academic and community sites in the US; all received at least 1 dose of epcoritamab. At a median follow-up of 7.6 months, 50.0% remained on treatment. For administration and planned monitoring, 81 of 88 patients were outpatient, and 7 of 88 were admitted, with 5 admitted for postdose monitoring and 2 for other reasons. Twenty-four of 81 patients monitored outpatient developed CRS within 1 week; the CRS hospitalization rate was 13.6% (11/81). Overall, CRS occurred in 40.2% of patients (grade 1-2: 38.0%; grade 3: 2.2%), and ICANS occurred in 7.6% (grade 1-2: 6.5%; grade 3: 1.1%). All CRS and ICANS events resolved without treatment discontinuation. The overall response rate per Lugano criteria was 62.0%, with a complete response rate of 42.4%. Efficacy results were consistent with prior results.²

Proactive vs reactive hospitalization. Sharman said the new FDA label allows physicians to avoid most “proactive” hospitalizations with the first full dose of epcoritamab, while acknowledging that some “reactive” hospitalizations will occur due to CRS or other adverse events. Of note, when asked what the chief concern was when evaluating patients for possible inpatient administration, Sharman said it was whether the patient had a competent caregiver.

“If those caregivers [are] trained on what to look for, when to report symptoms, and when to contact us, that's an important aspect,” he said. “On the other hand, patients lacking caregivers were often ones we might have admitted because they might not be able to self-report episodes of confusion or be aware of fevers. Similarly, [DLBCL] can be a rapidly moving disease, and sometimes patients can become very sick just from the disease itself. If a patient was really on the borderline as to whether they could be treated at all, sometimes those patients were admitted to the hospital [to be] treated.”

References

1. Caffrey M. FDA revises recommendation on first full epcoritamab dose in R/R DLBCL to allow outpatient monitoring. AJMC. April 1, 2026. Accessed April 8, 2026. https://www.ajmc.com/view/fda-revises-recommendation-on-first-full-epcoritamab-dose-in-r-r-dlbcl-to-allow-outpatient-monitoring
2. 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. Published online February 19, 2026. doi:10.1016/j.clml.2026.02.006
3. Caffrey M. Bispecifics in new combos, new uses, and earlier lines of treatment in myeloma. AJMC. December 15, 2025. https://www.ajmc.com/view/bispecifics-in-new-combos-new-uses-and-earlier-lines-of-treatment-in-myeloma
4. Diffuse large B-cell lymphoma (DLBCL) research. Blood Cancer United. Accessed April 13, 2026. https://bloodcancerunited.org/research/blood-cancer-research-development-progress/lymphoma/diffuse-large-b-cell-lymphoma-dlbcl