EHA Data for Epcoritamab Show Durable Responses in Older, Chemotherapy-Ineligible Patients With DLBCL

Presented at the recent European Hematology Association (EHA) 2026 Congress in Stockholm, Sweden, a pair of studies evaluating epcoritamab (Epkinly; Genmab/AbbVie)—a subcutaneous CD3×CD20 bispecific antibody—added to the drug's growing body of evidence in first-line treatment of diffuse large B-cell lymphoma (DLBCL).^1,2 Both trials targeted a population that has historically been underserved: elderly patients who are ineligible for standard anthracycline-based chemotherapy due to age or comorbidities. Results for EPCORE DLBCL-3 (NCT05660967) were simultaneously published in the Lancet Haematology.³

EPCORE DLBCL-3: Monotherapy in Patients Ineligible for Any Chemotherapy

EPCORE DLBCL-3 is a phase 2 trial evaluating fixed-duration epcoritamab monotherapy in patients with newly diagnosed CD20+ large B-cell lymphoma who are ineligible for anthracycline-based chemotherapy, either because they are 80 years or older or 75 years or older with significant comorbidities.¹ The trial enrolled 66 patients with a median age of 82.5 years (range, 76-95); 36% of the patients were 85 years or older. All had comorbidities, and 94% had 3 or more conditions at baseline. Nearly all patients (97%) had cardiovascular comorbidities. This population was high risk by multiple measures: 62% had Ann Arbor stage IV disease, 64% had an International Prognostic Index (IPI) score of 3 or higher, and 35% had bulky disease. Patients received epcoritamab with step-up dosing in cycle 1, followed by 48 mg weekly in cycles 1 to 3 and every 4 weeks in cycles 4 to 12, for up to 12 months.

With a median follow-up of 22 months, the overall response rate (ORR) was 73% among response-evaluable patients (n = 60), with 63% achieving a complete response (CR). The primary end point, CR rate in all enrolled patients, was 58% per investigator assessment. Responses came quickly, with a median time to response of 1.5 months and a median time to CR of 2.2 months. Responses deepened over time: 11 of 17 patients who had a partial response or stable disease at first assessment subsequently achieved a CR. Median duration of response (DOR) and duration of CR (DOCR) were not reached; an estimated 67% of responses and 73% of CRs were ongoing at 12 months. The median progression-free survival (PFS) was 13.0 months, and the median overall survival (OS) was not reached. At 18 months, an estimated 43% of patients remained progression-free, and 62% were alive.

Minimal residual disease (MRD) negativity was a notable finding: 92% of evaluable responders achieved MRD negativity at any time point, typically by day 1 of cycle 3, and this was sustained through day 1 of cycle 12 in most patients with available longitudinal samples.

The safety profile reflected the nature of this population. Cytokine release syndrome occurred in 71% of patients, though most events were low grade (grade 1: 38%; grade 2: 29%; grade 3: 5%), and 92% occurred in cycle 1. Immune effector cell–associated neurotoxicity syndrome was reported in 18% of patients (grade 1-2: 16%; grade 3: 3%). Infections of any grade occurred in 68% of patients, with 24% experiencing grade 3 or higher infections. Neutropenia was reported in 18%, with no febrile neutropenia or clinical tumor lysis syndrome. Eight treatment-emergent deaths occurred; 2 were considered treatment-related by the investigator.

“For newly diagnosed [older] patients with diffuse large B-cell lymphoma and comorbidities, who are often excluded from standard curative chemotherapy and ineligible for doxorubicin, finding more options is paramount,” Umberto Vitolo, MD, of Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Turin), Italy, said in a statement from Genmab.⁴ "The EPCORE DLBCL-3 study showed that epcoritamab monotherapy offers robust data. Importantly, its safety profile, including cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, was consistent with expected rates in this fragile population with a high unmet medical need for new therapeutic options.”

EPCORE NHL-2, Arm 8: Epcoritamab Plus R-Mini-CHOP

Arm 8 of the phase 1b/2 EPCORE NHL-2 trial (NCT04663347) assessed epcoritamab in combination with dose-attenuated R-CHOP (R-mini-CHOP), a standard-of-care regimen for older patients with newly diagnosed DLBCL who cannot tolerate full-dose R-CHOP, the well-known combination of rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine (Oncovin), and prednisone.

Eligible patients were either 75 years or older or 65 years or older with comorbidities. The 28-patient cohort had a median age of 81 years (range, 74-90), and the population was heavily pretreated by disease characteristics: 43% had IPI scores of 4 to 5, 64% had elevated lactate dehydrogenase, and 39% had bulky disease. Most patients (79%) completed treatment as planned.

With a median follow-up of 33.4 months, the ORR was 93%, and the CR rate was 86%. Median DOR, DOCR, PFS, and OS were all not reached. The estimated 2-year DOR and DOCR rates were both 79%, whereas estimated 2-year PFS and OS rates were 76% and 82%, respectively. These results compare favorably with historical outcomes for R-mini-CHOP alone, which have yielded 2-year PFS and OS rates of approximately 47% and 59%.

MRD negativity was achieved by 95% of evaluable patients at any time point, with 80% MRD negative by day 1 of cycle 3. High MRD negativity rates held up in high-risk subgroups, including patients with bulky disease (89%) and IPI scores of 3 to 5 (93%).

The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia (43%), serious infections (32%), and anemia (14%). The majority of serious infections occurred during the first 6 cycles, alongside R-mini-CHOP administration. Three patients (11%) discontinued epcoritamab due to TEAEs; 1 death involved a 90-year-old patient who experienced a confused state and cytomegalovirus reactivation in the context of an acute cerebrovascular accident.

References

1. Vitolo U, Burgues JMB, Duell J, et al. Fixed-duration epcoritamab monotherapy induces high response and MRD-negativity rates in elderly patients with newly diagnosed large B-cell lymphoma and comorbidities: results from EPCORE DLBCL-3. Presented at: EHA 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract 2346. https://library.ehaweb.org/eha/2026/eha-2026/4208633/umberto.vitolo.fixed-duration.epcoritamab.monotherapy.induces.high.response.html
2. Belada D, Duras J, Brody J, et al. Epcoritamab + R-Mini-CHOP results I 2-year remissions and high MRD-negativity rates in elderly patients with newly diagnosed DLBCL: results from the EPCORE NHL-2 trial. Presented at: EHA 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract 2359. https://library.ehaweb.org/eha/2026/eha-2026/4206896/david.belada.epcoritamab.2B.r-mini-chop.results.in.2-year.remissions.and.high.html
3. Vitolo U, Burgues JMB, Duell J, et al. Epcoritamab monotherapy or epcoritamab with lenalidomide as first-line therapy for patients with diffuse large B-cell lymphoma (EPCORE DLBCL-3): primary analysis of an open-label, multicentre, randomised, phase 2 trial. Lancet Hematol. 2026;13(7):e435-e448. doi:10.1016/S2352-3026(26)00112-2
4. Genmab announces epcoritamab monotherapy and epcoritamab-based combination regimens demonstrate high response rates in elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). News release. Genmab. June 13, 2026. Accessed June 25, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-epcoritamab-monotherapy-and-epcoritamab-based/