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ASH 2022: Lisaftoclax, an Experimental BCL-2 Inhibitor to Treat CLL / SLL

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Medically reviewed by Dr. Brian Koffman

The Bottom Line:

Lisaftoclax alone or combined with acalabrutinib or rituximab had a manageable safety profile and was active in patients with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL).

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 Annual Meeting 2022.


Lisaftoclax is an experimental BCL-2 inhibitor similar to venetoclax with a faster and more convenient ramp-up dosing. BCL-2 inhibitors bind to the BCL-2 protein, which is overexpressed in CLL / SLL, and block its action leading to cell death. Currently, lisaftoclax is being tested in clinical trials to assess its safety, tolerability, and efficacy.

In this video, Dr. Deborah Stephens, Director of the CLL and Lymphoma program at the University of Utah Huntsman Cancer Institute, interviewed Dr. Matthew Davids, Director of the Center for CLL at Dana-Farber Cancer Institute. They discussed updated results from a phase 1b clinical trial of lisaftoclax in patients with CLL / SLL.

Methods and Participants:

This study is a global, open-label, multicenter, two-part phase 1b dose-escalation and dose-expansion study to assess the safety and tolerability of lisaftoclax alone or in combination with acalabrutinib or rituximab. See our previous coverage of a phase 1b study of lisaftoclax for more details.


  • 164 patients with relapsed/refractory or treatment-naïve CLL / SLL have been enrolled in the study thus far.
  • Side effects were typical of what has been seen with this class of drugs, including low white blood cell counts (30%), anemia (24%), diarrhea (20%), and low platelet counts (17%).
  • Four patients out of 164 (2%) experienced tumor lysis syndrome, which is a condition that occurs when a large number of cancer cells die within a short period of time. Two patients had clinical symptoms, while the other two patients only had changes in lab values that resolved quickly.
  • Due to the timing of this study (it started early in the COVID-19 pandemic) and the fact it was conducted in several different countries, there were quite a few COVID-19 cases (26%), including eight deaths dues to COVID-19.
  • No patients discontinued the study due to lisaftoclax or combination therapy, and no dose-limiting toxicities were observed.
  • Nineteen patients discontinued due to progressive disease, of which 18 were on monotherapy; 4 patients withdrew consent; 2 had a second primary malignancy; 2 had an infection; and ten patients died (8 due to COVID-19 infections as well as one multiorgan failure, and one unknown cause, both unrelated to therapy).
  • The overall response rates were 65% for lisaftoclax monotherapy, 87% for lisaftoclax plus rituximab, and 98% for lisaftoclax plus acalabrutinib.


Lisaftoclax alone or combined with acalabrutinib or rituximab had a manageable safety profile and was active in patients with treatment-naïve or relapsed/refractory CLL / SLL. Thus far, the daily dose ramp-up appears to be feasible and safe. A larger phase 3 clinical trial is planned to further test lisaftoclax in combination with acalabrutinib in more patients.

Links and Resources:

Watch the interview on the abstract here:

ASH 2022: Dr. Matthew Davids on Lisaftoclax for Chronic Lymphocytic Leukemia Treatment

You can read the actual ASH abstract here: Lisaftoclax (APG-2575) Safety and Activity As Monotherapy or Combined with Acalabrutinib or Rituximab in Patients (pts) with Treatment-Naïve, Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (R/R CLL / SLL): Initial Data from a Phase 2 Global Study.

Take care of yourself first.

Ann Liu, PhD