Adding the bispecific antibody epcoritamab (epkinly; AbbVie/Genmab) to the combination of rituximab (Rituxan) and lenalidomide (Revlimid) offers a huge leap in efficacy for patients who have had their first relapse in follicular lymphoma (FL), one that a trial investigator described as a “new benchmark” in treatment that would make its way into community practise.
Lorenzo Falchi, MD, lymphoma specialist at Memorial Sloan Kettering Cancer Center, presented results early Sunday in press conference for the phase 3 EPCORE FL-1 trial (NCT05409066), which evaluated a fixed-duration regimen of epcoritamab, rituximab, and lenalidomide against rituximab and lenalidomide alone, a combination known as R2.
Lorenzo falchi,MD | image: MSK
For EPCORE FL-1,668 patients screened for eligibility across 189 sites in 30 countries,which included those in Africa,Asia,Australia,Europe,North America,and South America. A total of 488 participants were randomly assigned to epcoritamab plus R arm (243 patients) and R-only arm (245 patients).
Results for the 2 coprimary end points were as follows:
* Adding epcoritamab to R2 significantly improved progression-free survival (PFS) with a hazard ratio (HR) of 0.33 (95% CI, 0.24-0.45; *P* < .0001). The median PFS was not yet reached in the epcoritamab arm versus 14.1 months in the R2 arm.
* epcoritamab plus R2 demonstrated a statistically significant and clinically meaningful betterment in overall survival (OS) with an HR of 0.46 (95% CI, 0.30-0.70; *P* = .0002). The median OS was not yet reached in the epcoritamab arm versus 34.8 months in the R2 arm.## Epcoritamab Plus Chemotherapy Shows Promise in Relapsed/Refractory DLBCL
Fixed-duration epcoritamab plus chemotherapy has demonstrated encouraging response and remission rates in patients with relapsed or refractory diffuse large B-cell lymphoma4-6. This finding addresses the critical need for more effective treatments while maintaining accessibility for patients.
The regimen strikes a balance between potent therapy and convenient, community-based care.As bispecific antibody governance expands into community settings, this approach appears especially well-suited for patients experiencing relapse.
Study results indicated consistent benefits across various patient subgroups, including those identified as high-risk and low-risk, alongside a manageable safety profile within a fully outpatient setting.
While the epcoritamab plus R2 arm exhibited a higher incidence of adverse events (AEs), with grade 3 or higher AEs observed in 90% of participants compared to 68% in the R2-only arm, cytokine release syndrome remained low grade. Specifically,21% experienced grade 1 CRS and 5% had grade 2,with all events resolving.
The fixed-duration nature of the 12-cycle epcoritamab plus R2 regimen aligns with a growing trend in oncology towards therapies that prioritize quality of life. This novel chemotherapy-free approach, as Falchi noted, offers a promising new option for patients.
Epcoritamab Shows Promise in Aggressive Lymphoma and Follicular Lymphoma: 3-Year Trial Results
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New data presented at the 67th American Society of Hematology (ASH) Annual meeting & Exposition in December 2025 demonstrate the sustained efficacy and manageable safety of epcoritamab,an innovative bispecific antibody,in treating both Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL). These results from the EPCORE NHL-2 trial highlight epcoritamab’s potential to significantly improve outcomes for patients with these blood cancers, particularly those with high-risk features or who are elderly.
What is Epcoritamab?
Epcoritamab is a CD20-targeted bispecific antibody. This means it’s engineered to bind to two different targets: the CD20 protein found on lymphoma cells and the CD3 protein found on T cells. By bringing these two immune cells together, epcoritamab activates the T cells to kill the lymphoma cells. [https://www.abbvie.com/newsroom/news-releases/2023/08/21/abbvie-and-genmab-announce-fda-approval-of-epkinly-epcoritamab-mab-bysp-for-adult-patients-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma]
Epcoritamab in newly Diagnosed DLBCL
The EPCORE NHL-2 trial investigated epcoritamab in combination with standard chemotherapy regimens for patients with newly diagnosed DLBCL. Specifically, the trial focused on patients with high International Prognostic Index (IPI) scores (3-5), indicating a more aggressive disease course.
* Epcoritamab + R-CHOP: Combining epcoritamab with the standard R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) resulted in sustained remissions and disease-free survival extending beyond three years. [ASH Abstract 1955]
* Epcoritamab + R mini-CHOP: For elderly patients, a reduced-intensity chemotherapy regimen (R mini-CHOP) combined with epcoritamab led to two-year remissions and high rates of minimal residual disease (MRD) negativity, suggesting a deep and durable response. [ASH abstract 64] MRD negativity means that after treatment, there are no detectable cancer cells remaining, which is a strong predictor of long-term remission.
These findings suggest that epcoritamab can enhance the effectiveness of chemotherapy, even in patients with challenging disease characteristics.
Epcoritamab in Follicular Lymphoma
The trial also evaluated epcoritamab in combination with bendamustine and rituximab for the first-line treatment of follicular lymphoma (FL).
* Deep and Durable Responses: Three-year results demonstrated deep and durable responses with manageable safety profiles. [ASH Abstract 5357] This indicates that the combination therapy can lead to long-lasting remission in patients with FL.
Safety Considerations
While the trial results are promising, it’s significant to note that, like all cancer treatments, epcoritamab can have side effects. The presented data indicated manageable safety profiles across all treatment arms, but detailed safety data will continue to be analyzed and reported.
Key Takeaways
* Epcoritamab demonstrates significant efficacy when combined with chemotherapy in both DLBCL and FL.
* The treatment shows promise for patients with high-risk DLBCL (IPI 3-5) and elderly patients.
* Long-term follow-up data (up to 3 years) support the durability of responses.
* The safety profile appears manageable.
Looking Ahead
The EPCORE NHL-2 trial results represent a significant step forward in the treatment of aggressive lymphomas and follicular lymphoma. Further research will focus on optimizing treatment regimens, identifying biomarkers to predict response, and exploring the potential of epcoritamab in other lymphoma subtypes. The continued development of bispecific antibodies like epcoritamab offers hope for improved outcomes and a better quality of life for patients battling these challenging cancers.
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