Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, (MDCM )retired, MSEd
The Bottom Line:
Lisaftoclax was well-tolerated and active in patients with CLL / SLL, and the combination of lisaftoclax plus acalabrutinib is effective.
Who Performed the Research and Where Was it Presented:
Dr. Matthew Davids from Dana-Farber Cancer Institute and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
B-cell lymphoma 2 (BCL2) inhibitors are very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). They are so good at killing cancer cells that they can cause tumor lysis syndrome. In this condition, cells die so rapidly that the kidneys can’t clear the debris fast enough, leading to potentially dangerous electrolyte imbalances. Because of this risk, venetoclax is usually ramped up slowly over five weeks, potentially with an inpatient stay for high-risk patients. Lisaftoclax is an experimental BCL2 inhibitor that can be ramped up over five days rather than five weeks. It has been tested in a phase 1/2 clinical trial, which we previously reported on, and here researchers presented updated results.
Methods and Participants:
This is a phase 1b/2 study of lisaftoclax alone or combined with acalabrutinib or rituximab in patients with treatment-naïve or relapsed / refractory CLL / SLL. Patients received daily oral lisaftoclax alone or in combination with continuous acalabrutinib or six cycles of rituximab.
Results:
- A total of 176 patients enrolled in the trial; 88% were relapsed / refractory and 12% were treatment-naïve.
- 49 patients received lisaftoclax alone, 39 received lisaftoclax plus rituximab, and 91 received lisaftoclax plus acalabrutinib.
- Tumor lysis syndrome occurred in 5 patients (3%), and all cases were mild and manageable; patients were able to continue with treatment.
- Lisaftoclax was generally well-tolerated, and side effects were similar to those seen with venetoclax, including low neutrophil counts (34%), mild diarrhea (22%), anemia (15%), and low platelet counts (13%).
- The overall response rate for lisaftoclax plus acalabrutinib was 96%, and 1.5 years later, the progression-free survival rate was 86%.
- Patients who had previously been treated with venetoclax had a good overall response rate (86%) to lisaftoclax plus acalabrutinb.
Conclusions:
Lisaftoclax was well-tolerated and active in patients with CLL / SLL, and the combination of lisaftoclax plus acalabrutinib appears to be effective. The five-day ramp-up was feasible with close monitoring and is an attractive option for both patients and healthcare providers. Lisaftoclax is moving on to testing in a phase 3 clinical trial. The GLORA study will compare combination lisaftoclax plus acalabrutinib with acalabrutinib alone. If you are interested in participating, more information can be found here: Global Trial in APG2575 for Patients With CLL/SLL.
Links and Resources:
Watch the interview on the abstract here:
You can read the ASH abstract here: Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given with Accelerated Ramp-up and then Combined with Acalabrutinib or Rituximab in Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL / SLL), Including Those with Prior Exposure to Venetoclax
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