EPCORE CLL-1: An Advance in Treating Relapsed/Refractory Chronic Lymphocytic Leukemia With Alexey Danilov, MD, PhD
Expert Perspectives · Lyn Brook · 2024-12-19
Alexey Danilov, MD, PhD, a Professor in Hematology at City of Hope National Medical Center, presented findings from the EPCORE CLL-1 trial at the 2024 American Society of Hematology (ASH) Annual Meeting. This trial investigates the efficacy and safety of epcoritamab, a CD3-CD20 bispecific antibody, in treating patients with double-refractory chronic lymphocytic leukemia (CLL)—those who have failed BTK inhibitors and venetoclax therapy.
Challenges in Double-Refractory CLL Treatment
Patients with double-refractory CLL face limited therapeutic options, with suboptimal outcomes from existing treatments like chimeric antigen receptor (CAR) T-cell therapy, which is often associated with cytokine release syndrome (CRS), neurotoxicity, and infections. Epcoritamab, previously approved for follicular and diffuse large B-cell lymphoma, is being explored for its potential in CLL.
EPCORE CLL-1 Trial Design
The study enrolled 40 patients with relapsed/refractory CLL, most of whom had high-risk genetic mutations like TP53 abnormalities. Two cohorts were examined: the expansion cohort used a two-step dosing regimen, and the optimization cohort employed a three-step regimen to reduce CRS risk. Both cohorts incorporated dexamethasone prophylaxis and hydration to mitigate side effects.
Key Findings
- Safety Profile: The optimization cohort showed significantly reduced CRS incidence, with no grade 3 CRS or neurotoxicity cases. Common adverse events included anemia, neutropenia, and fatigue
- Efficacy: The trial reported a 61% overall response rate and a 39% complete response rate. Efficacy was consistent across all subgroups, including patients with high-risk genetic features and those exposed to prior intensive therapies
- Durability: The median progression-free survival was approximately 13 months
Implications for CLL Treatment
Epcoritamab represents a novel and effective therapeutic option for heavily pretreated CLL patients. Dr. Danilov emphasized its potential utility in earlier treatment lines, suggesting it could achieve deeper and longer-lasting responses in patients with less compromised immune systems.
Future Directions
Ongoing studies aim to explore epcoritamab in combination with BTK inhibitors and venetoclax for less heavily pretreated populations. Discussions are also underway to incorporate epcoritamab into earlier treatment settings, where its efficacy could be maximized.
Guidance for Patients
Dr. Danilov encouraged patients to seek second opinions and explore clinical trial opportunities, particularly those involving novel agents like epcoritamab. He stressed that clinical trials offer access to cutting-edge treatments that can significantly improve outcomes for challenging cases of CLL.
Epcoritamab’s promising results position it as a potentially transformative option in the management of relapsed/refractory CLL, addressing a critical unmet need for this patient population.
About Dr. Danilov
Alexey Danilov, MD, PhD, is a Professor in Hematology at City of Hope National Medical Center, as well as a clinical trialist and translational investigator. Dr. Danilov is internationally recognized for his expertise in research of chronic lymphocytic leukemia, mantle cell lymphoma, and non-Hodgkin lymphoma. In addition, he is a Leukemia & Lymphoma Society Scholar and serves as the Principal Investigator on several grants from the National Cancer Institute.