The Bottom Line:
Early results from a phase 1b/2 trial show that epcoritamab has a manageable safety profile and an encouraging response rate in patients with Richter’s syndrome. It is still very early in the trial, so we will wait to see if these results hold as the trial progresses.
Who Performed the Research and Where Was it Presented:
Dr. Arnon Kater from Cancer Center Amsterdam and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Background:
Richter’s transformation, also called Richter’s syndrome, occurs when CLL / SLL changes into a related but much more aggressive type of large B-cell lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Richter’s transformation is quick-moving and challenging to treat, and it remains one of the most significant unmet needs in CLL.
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. We previously reported on the safety of epcoritamab in patients with relapsed/refractory CLL, and this article, Dr. Lindsey Roeker on Epcoritamab, a Bispecific Antibody for Relapsed Chronic Lymphocytic Leukemia (CLL), offers a simple basic explanation on how epcoritamab works and the trial design.
In this video, Dr. Javier Pinilla, Senior Member and Head of the Lymphoma Section at Moffitt Cancer Center interviewed Dr. Arnon Kater, a hematologist at Amsterdam UMC in the Netherlands. They discussed the latest results from the EPCORE CLL-1 trial, evaluating the safety and efficacy of epcoritamab in patients with relapsed/refractory CLL / SLL or Richter syndrome.
Methods and Participants:
The EPCORE CLL-1 trial is an open-label, multicenter, phase 1b/2 trial evaluating the safety and efficacy of epcoritamab in adults with relapsed/refractory CLL or Richter’s syndrome. For this cohort, eligible patients had biopsy-confirmed Richter’s syndrome and no more than one prior therapy for Richter’s syndrome. Epcoritamab was administered as subcutaneous injections weekly in cycles 1-3, every two weeks in cycles 4-9, and once a month in cycles ≥10 (28 d/cycle) until disease progression or unacceptable toxicity.
Results:
- Thus far, 10 patients with Richter’s syndrome have received epcoritamab 48 mg with a follow-up of ≥12 weeks.
- Prior therapies included rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), and rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP), and 6 patients received epcoritamab as first-line therapy for Richter syndrome.
- The most common related treatment-emergent adverse events were cytokine release syndrome (90%), anemia (40%), diarrhea (40%), low blood phosphorous levels (30%), injection-site reaction (30%), and low blood platelets (30%).
- No cases of neurotoxicity (ICANS) were observed.
- Tumor lysis syndrome occurred in one patient and resolved within three days.
- No adverse events led to treatment discontinuation.
- The overall response rate was 60%, and the complete response rate was 50%, but it is early on in the study, so it remains to be seen if these responses are durable.
- It takes approximately 1-2 months to see a response.
Conclusions:
Thus far, epcoritamab has demonstrated a manageable safety profile and an encouraging response rate in patients with Richter’s syndrome. However, it is still very early in the trial, so we will wait to see if these results hold as the trial progresses. If you are interested in participating in the study, more information can be found here.
Immunotherapies such as monoclonal antibodies, including rituximab and obinutuzumab, have significantly improved outcomes for those with CLL / SLL and Richter’s syndrome. There is reason to be hopeful that these newer two-pronged antibodies will provide another giant step forward.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Subcutaneous Epcoritamab in Patients with Richter’s Syndrome: Early Results from Phase 1b/2 Trial (EPCORE CLL-1)
Take care of yourself first.
Ann Liu, PhD
