Epcoritamab: A New Era in Lymphoma Treatment and What’s Next
Recent data published in Annals of Hematology reveal promising long-term outcomes for patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with epcoritamab (Epkinly; Genmab/AbbVie). The EPCORE NHL-1 trial demonstrates that over half of patients achieving a complete response (CR) remained in remission at three years, with 63% still alive. These findings build on earlier approvals and signal a potential shift in how we approach aggressive lymphomas.
Durable Remission Rates and Patient Characteristics
The EPCORE NHL-1 trial enrolled 157 patients with relapsed or refractory CD20+ mature B-cell lymphoma, including 139 with diffuse large B-cell lymphoma (DLBCL). A significant portion of these patients – 75% – had previously failed at least two lines of treatment, and nearly 40% had already undergone CAR T-cell therapy. Despite this heavily pretreated status, epcoritamab demonstrated remarkable efficacy.
At the three-year mark, the overall response rate (ORR) stood at 59%, with a CR rate of 41%. Importantly, these rates remained stable over time, suggesting sustained benefit. Median duration of complete response reached 36.1 months, one of the longest durations observed for approved bispecific antibodies in this patient population. Measurable residual disease (MRD) negativity was achieved in 45% of evaluable patients.
Expanding Applications: From Relapsed Disease to First-Line Potential
Epcoritamab’s journey began with FDA accelerated approval in May 2023 for relapsed/refractory DLBCL, followed by approval for follicular lymphoma (FL) in June 2024. However, the landscape is rapidly evolving. In November 2025, the FDA approved epcoritamab in combination with lenalidomide and rituximab (R2) for FL as early as the first relapse, based on the EPCORE FL-1 trial.
This progression highlights a growing trend: moving bispecific antibodies earlier in the treatment paradigm. The initial focus was on salvaging patients who had exhausted other options. Now, the data suggest a role for these therapies in achieving deeper, more durable remissions, potentially even in the first-line setting for select patients.
Safety Profile and Manageable Side Effects
Long-term safety data from the EPCORE NHL-1 trial are consistent with previous reports. Cytokine release syndrome (CRS) remains the most common adverse event, occurring in 51% of patients, but most cases were low-grade and manageable, particularly with early intervention. Infections were reported in 57% of patients, with the majority being grade 1 or 2. COVID-19 contributed to some grade 3 or higher infection-related adverse events.
Ongoing Research and Future Directions
Genmab and AbbVie are actively investigating epcoritamab in multiple phase 3 trials, both as a monotherapy and in combination with other treatments. The recent topline results from the EPCORE DLBCL-1 trial, showing a 26% improvement in progression-free survival (PFS) compared to chemoimmunotherapy, further solidify epcoritamab’s potential. While overall survival did not reach statistical significance in this trial, the PFS benefit and improvements in complete response rates, duration of response, and time to next treatment are encouraging.
Did you realize? Bispecific antibodies like epcoritamab represent a fundamentally different approach to cancer treatment, harnessing the power of the patient’s own immune system to target and destroy cancer cells.
FAQ
What is epcoritamab? Epcoritamab is a bispecific antibody that targets both CD3 on T-cells and CD20 on lymphoma cells, bringing the immune system closer to the cancer to eliminate it.
What is the significance of MRD negativity? Achieving measurable residual disease negativity suggests a deeper level of remission and is often associated with improved long-term outcomes.
What are the common side effects of epcoritamab? The most common side effects include cytokine release syndrome and infections, which are generally manageable.
Is epcoritamab a cure for lymphoma? While epcoritamab has shown remarkable efficacy in achieving durable remissions, it is not yet considered a cure. Ongoing research is focused on optimizing treatment strategies and identifying patients who are most likely to benefit.
Pro Tip: Patients considering epcoritamab should discuss their individual risk factors and treatment goals with their oncologist to determine if it is the right option for them.
Stay informed about the latest advancements in lymphoma treatment. Explore additional resources on non-Hodgkin lymphoma and related therapies.
What questions do you have about epcoritamab and its potential impact on lymphoma care? Share your thoughts in the comments below!
