At the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 883), Alexey Danilov, MD, PhD, of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope National Medical Center, Duarte, California, reported that single-agent epcoritamab led to “encouraging” complete response and undetectable measurable residual disease (MRD) in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
“To date, no treatments have been shown in randomized trials to be effective for patients whose CLL has worsened after treatment with both BTK and BCL2 inhibitors,” he said. “There is an unmet need for new treatment options for this group of patients.”
Epcoritamab, which is given subcutaneously, belongs to a class of drugs known as bispecific T-cell engagers. They work by attaching to proteins on the surfaces of both cancer cells and healthy T cells. Epcoritamab is approved by the U.S Food and Drug Administration to treat two types of resistant lymphoma (diffuse large B-cell lymphoma and follicular lymphoma).
Alexey Danilov, MD, PhD
“CLL cells have learned how to persist in the body by making themselves invisible to the patient’s immune system,” Dr. Danilov said. “Epcoritamab essentially works as a bridge between the body’s immune cells and the CLL cells, boosting the ability of the immune cells to find, attack, and kill the cancer cells.”
Study Details
The ongoing EPCORE CLL-1 trial is testing the effectiveness of epcoritamab in patients with refractory CLL and other hematologic malignanciesa. The trial, which is being conducted in 12 countries, will enroll a total of 184 patients.
The current study reports early results for the first 40 patients (median age, 71.5 years, mostly male) enrolled in the trial. Most had CLL with TP53 mutation. The first group (the fully enrolled CLL expansion cohort [EXP], 23 patients) received epcoritamab in three gradually increasing doses, whereas the second group (the cycle 1 optimization cohort [OPT] cohort, 17 patients), who were enrolled later, received it in four increasing doses.
The primary endpoint for the EXP cohort was the overall response rate. Secondary endpoints included the time until patients’ cancer showed signs of worsening, overall survival, and MRD. For the OPT cohort, the primary endpoints included the number and severity of new cases of common side effects.
Key Results
In the EXP cohort, after a median follow-up of 22.8 months, the overall response rate was 61%. Among responding patients, 39% had a complete response. For all patients in this cohort, the median time until their cancer showed signs of worsening was 12.8 months. After about 15 months of follow-up, an estimated 65% of patients (15 people) were still alive. Among 12 responding patients (52%) who underwent MRD testing, 9 (75%) had undetectable MRD in tests based on the standard sensitivity level.
“The response rate was very impressive for a single agent, especially considering that most patients had already been treated with both BTK and BCL2 inhibitors without success and had disease features that are difficult to treat,” Dr. Danilov said.
Low blood cell counts were common in patients in the EXP cohort. However, most patients had low blood cell counts when they enrolled in the study. Cytokine-release syndrome (CRS) was the most frequent non-blood–related adverse effect, occurring in 96% of patients. In most cases, CRS was mild, Dr. Danilov said, and most occurred after the first full dose of epcoritamab. Other common side effects were diarrhea, fatigue, and swelling in the hands or lower legs. Four patients in the EXP cohort (17%) died, all of causes other than CLL.
Follow-up for patients in the OPT cohort, who were enrolled in the study later than those in the EXP cohort, was 2.9 months. Because of the brevity of follow-up to date, data on the effectiveness of epcoritamab treatment in this cohort are not yet available, Dr. Danilov said. A total of 84% had mild CRS; none had severe CRS. To date, no patients in the OPT cohort have died. No patients in either cohort have discontinued treatment because of adverse effects, according to Dr. Danilov.
He cautioned that these are early results from just 40 patients. “We will need to treat more patients, follow them for a longer period of time, and conduct randomized studies to validate these findings,” Dr. Danilov said. “We also want to test epcoritamab in patients with CLL who have had fewer prior therapies. There is reason to believe it could be even more effective if used earlier in the disease course, when a patient’s immune system is less compromised.”
Disclosure: This study was funded by GenMab, co-developer of epcoritamab with AbbVie. For full disclosures of the study authors, visit ash.confex.com.
