Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman (MDCM ), retired. MSEd
The Bottom Line:
Epcoritamab in combination with either lenalidomide or R-CHOP produced complete responses in more than half of patients with Richter transformation.
Who Performed the Research and Where Was it Presented:
Dr. Philip Thompson from the Sir Peter MacCallum Cancer Center and the University of Melbourne, and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Richter transformation is a rare transformation of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) into a fast-growing, aggressive lymphoma, usually DLBCL (diffuse large B-cell lymphoma). Chemotherapy regimens such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) are often used to treat DLBCL, but Richter transformation is largely resistant to these types of treatment. As a result, patient outcomes are poor, with most patients living less than one year after diagnosis. New therapies are greatly needed.
Researchers are investigating whether the body’s own immune system can help fight Richter transformation. Epcoritamab is part of a new experimental class of immunotherapy drugs known as bispecific antibodies, which work by bringing your immune cells in close proximity to cancer cells. Epcoritamab binds to T cells and then brings the T cell over to the CLL cell to destroy it. When epcoritamab is used by itself in patients who have not been treated for Richter transformation before, about half of the patients achieve a complete response. Researchers wanted to know whether combining epcoritamab with other therapies would make it even more effective.
Methods and Participants:
This study was part of a larger phase 1b/2 trial testing the efficacy of epcoritamab in patients with relapsed / refractory CLL and Richter transformation. In these study arms, patients with Richter transformation received as frontline or second-line therapy either:
- Epcoritamab plus lenalidomide. Lenalidomide is an immunotherapy that is thought to improve T cell function and immune response.
- Epcoritamab plus R-CHOP. R-CHOP is a chemoimmunotherapy combination that is commonly used as a first-line treatment for Richter transformation.
Results:
- Eleven patients received epcoritamab plus lenalidomide.
- With a median follow-up of 13 months, the overall response rate (how many patients had their cancer shrink) was 82%, and the complete response rate (how many patients had no detectable signs of cancer) was 73%.
- Common side effects included cytokine release syndrome (100%), low neutrophil counts (82%), low platelet counts (73%), anemia (45%), and low potassium levels (45%).
- Thirty patients received epcoritamab plus R-CHOP.
- With a median follow-up of 10 months, the overall response rate was 73%, and the complete response rate was 60%.
- Common side effects included cytokine release syndrome (60%), anemia (60%), low neutrophil counts (60%), diarrhea (33%), and low neutrophil counts accompanied by fever (30%).
- It is still early in the study, so researchers are still following patients to see how durable the responses are.
Conclusions:
Epcoritamab in combination with lenalidomide or R-CHOP produced complete responses in more than half of patients with Richter transformation. This is really encouraging data, especially when the current standard treatment, R-CHOP by itself, only produces complete responses in around 20% of patients. The side effects were largely manageable and in line with what has already been seen with these therapies individually. A longer follow-up will give us more information on whether these responses are durable.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Epcoritamab combinations demonstrate promising efficacy in patients (pts) with Richter transformation (RT): First results from arms 2B (epcor + lenalidomide [LEN]) and 2C (epcor + R-CHOP) of the phase 1b/2 EPCORE CLL-1 trial
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