Data Show Epcoritamab Plus R-DHAX/C Can Be a Bridge to ASCT in R/R DLBCL

During the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025, investigators presented a bounty of results from EPCORE-NHL-2 (NCT04663347), the phase 1b/2, open-label, multicenter study evaluating multiple uses and combinations of epcoritamab (Epkinly; Genmab/AbbVie).¹

This subcutaneous CD3×CD20 bispecific antibody is FDA approved on its own to treat relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and in combination with lenalidomide and rituximab for R/R follicular lymphoma (FL).² Results from 5 different arms of EPCORE-NHL-2 presented at ASH 2025 showed strong responses for epcoritamab in combinations across different patient groups.¹ Now, data presented this week from arm 4 show epcoritamab’s potential in a different role: as a bridge to autologous stem cell transplant (ASCT).³

Published in Haematologica, the findings report on use of epcoritamab in patients with R/R DLBCL who are eligible for high-dose therapy (HDT) followed by ASCT. This regimen can be curative in patients who relapse 12 months after their initial treatment—if they have a good response to salvage chemoimmunotherapy. However, only 40% to 60% of patients achieve an overall response and only about half make it to ASCT.³

“The treatment of R/R DLBCL remains challenging, with inadequate responses to salvage chemoimmunotherapy limiting patients’ ability to receive potentially curative treatments like [ASCT],” the authors write.³

The new data from arm 4 of EPCORE-NHL-2 show that combining epcoritamab with rituximab, dexamethasone, cytarabine, and oxaliplatin/carboplatin, or R-DHAX/C, produced strong responses in HDT-ASCT–eligible patients with CD20-positive R/R DLBCL. Of note, 55% proceeded to ASCT after the regimen, with 88% of transplanted patients in complete response (CR) at the time of transplant. Another 5 patients choose to stay on epcoritamab monotherapy rather than proceeding to ASCT, and all achieved a CR.

Study Design. Patients received a 48-mg dose of subcutaneous epcoritamab weekly during three 21-day cycles alongside standard R-DHAX/C chemotherapy. Following combination treatment, epcoritamab monotherapy continued until ASCT or disease progression. To be eligible, patients had received at least 1 prior line of therapy and had measurable disease. The primary end point was investigator-assessed overall response rate (ORR) by Lugano criteria.

Twenty-nine patients were enrolled between February and September 2021. Among those enrolled, 72% had stage IV disease, 66% had primary refractory disease, 83% had progressed within 12 months of first-line therapy, and 26% had double-hit or triple-hit lymphoma. Of note, 10% previously received chimeric antigen receptor (CAR) T-cell therapy.

Results. After a median follow-up of 40.4 months, with data cutoff at January 15, 2025. Results were as follows³:

• Epcoritamab plus R-DHAX/C produced an ORR of 79% and a CR rate of 69% across all 29 patients.
• Median time to response was 1.4 months and median time to CR was 1.5 months, with many responses evident at the first scheduled assessment at week 6.
• Of the 29 patients, 21 (72%) completed the planned combination treatment per protocol. Sixteen patients (55%) proceeded to ASCT, with 88% in CR at the time of transplant.
• Of the 5 patients who opted to continue on epcoritamab instead of ASCT, 3 of 5 had sustained a CR at data cutoff, with duration of response beyond 35 months.
• At 36 months, 70% of responders remained in response, and median progression-free survival was not reached; 76% of all patients were still alive.
• Among patients who received ASCT, 83% remained in response; median overall survival was not reached at 36 months.
• Eight patients stopped treatment early, primarily due to disease progression. Outcomes were poor; 7 patients died before data cutoff.

Safety data were consistent with known effects of both epcoritamab and the R-DHAX/C regimen. All 29 patients experienced at least 1 treatment-emergent adverse event (TEAE), and 97% had grade 3 or 4 events. The most common TEAEs were thrombocytopenia (90%), anemia (66%), neutropenia (59%), and nausea (52%).³

Cytokine release syndrome (CRS) occurred in 45% of patients, but all events were low grade (grade 1-2), most commonly presenting as fever, and resolved within a median of 2 days; no patient discontinued treatment due to CRS. One patient experienced grade 2 immune effector cell–associated neurotoxicity syndrome, which resolved but led to epcoritamab discontinuation. No fatal TEAEs and no clinical tumor lysis syndrome events were observed. The authors note that 44% (7 of 16) of transplanted patients required plerixafor for stem cell mobilization, but all were ultimately successfully mobilized and none failed to proceed to ASCT.³

The main limitations cited were the study’s small size and single-arm design. Still, the authors wrote that results support the possible use of bispecific antibodies and epcoritamab in particular as a key component in salvage regimens, especially when CAR T-cell therapy is not easily accessible. Besides more than half of patients proceeding to ASCT, there was long-term disease control and a manageable safety profile. Combined with efficacy outcomes that compare favorably with trials such as ZUMA-7 and TRANSFORM, they wrote, “these results support the potential benefit of adding epcoritamab to salvage therapy regimens and warrant further evaluation in larger, controlled studies.”³

References

1. Genmab to showcase latest blood cancer treatment advancements at 2025 American Society of Hematology (ASH) Annual Meeting. News release. Genmab. November 3, 2025. Accessed March 11, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-showcase-latest-blood-cancer-treatment-advancements-2025
2. Caffrey M. EPCORE FL-1: adding epcoritamab to R2 delivers “new benchmark” in second-line follicular lymphoma. Am J Manag Care. 2026;32(Spec. No. 1):SP30. https://www.ajmc.com/view/epcore-fl-1-adding-epcoritamab-to-r2-delivers-new-benchmark-in-second-line-follicular-lymphoma
3. Abrisqueta P, Karimi YH, Morillo D, et al. Epcoritamab plus rituximab, dexamethasone, cytarabine, oxaliplatin/carboplatin induces deep and durable responses in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma: results from the EPCORE NHL-2 trial. Haematologica. Published online March 5, 2026. doi:10.3324/haematol.2025.300086