Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman (MDCM ), retired. MSEd
The Bottom Line:
Half of patients with Richter transformation responded to treatment with epcoritamab, and outcomes were even better when it was used as a first-line therapy.
Who Performed the Research and Where Was it Presented:
Dr. Arnon Kater from Amsterdam UMC 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 an aggressive lymphoma, usually DLBCL (diffuse large B-cell lymphoma). There is currently no established standard of care for Richter transformation, and outcomes are poor, with most patients living less than one year after diagnosis. New therapies are greatly needed.
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. Here, researchers report the 2-year follow-up results of a clinical trial of epcoritamab in patients with Richter transformation.
Methods and Participants:
The EPCORE CLL-1 study is a phase 1b/2 clinical trial, which is evaluating the clinical efficacy and safety of epcoritamab in both relapsed / refractory CLL and Richter transformation. The study included patients with CD20+ DLBCL who had a history of CLL or SLL and who had received two or fewer prior lines of therapy for Richter transformation. Epcoritamab was given until disease progression or unacceptable toxicity.
Results:
- Forty-two patients with Richter transformation were treated with epcoritamab, and for half of these patients it was their first therapy for Richter transformation.
- With a median follow-up of 23 months, the overall response rate (how many patients had their cancer shrink) was 48%, and 40% of patients had a complete response.
- The median duration of response was approximately 10 months.
- Median progression-free survival (amount of time before the disease worsens) was 3 months, and median overall survival (amount of time patients live) was 13 months.
- Patients who received epcoritamab as a first-line therapy had better responses (complete response in 52% of patients) and better outcomes (progression-free survival of 9 months and overall survival of 28 months).
- The most common side effects were cytokine release syndrome (86%), infection (74%), anemia (50%), low platelets (48%), low neutrophils (45%), diarrhea (36%), and fatigue (31%).
- Cytokine release syndrome is a known side effect of immunotherapies, which causes flu-like symptoms, and most cases were mild and easily managed.
- Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 12% of patients, and all cases were mild.
Conclusions:
Half of patients with Richter transformation responded to treatment with epcoritamab, and outcomes were even better when it was used as a first-line therapy. These are encouraging results in a notoriously difficult-to-treat disease. Combining it with other therapies may enhance its efficacy, and these trials are planned and ongoing. It is clearly a very active drug in both CLL and Richter transformation, but its continuing development for both FDA approvals for these indications is far from certain.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Epcoritamab monotherapy demonstrates promising efficacy in patients with Richter transformation (RT): 2-year follow-up results from arm 2A of the phase 1b/2 EPCORE CLL-1 trial
