What follows is our patient-friendly summary of this research.
The Bottom Line:
Lisaftoclax is an experimental BCL-2 inhibitor similar to venetoclax with a faster and more convenient ramp-up dosing.
By whom and where was the research done and presented:
Jianyong Li from Jiangsu Province Hospital, Nanjing, China, and others presented the results of their multicenter study done in China at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago in 2022.
Chronic lymphocytic leukemia, or CLL cells, evades programmed death or apoptosis by overexpressing BCL-2 proteins. Venetoclax blocks that overexpression leading to rapid cell death. It is the only approved BCL-2 inhibitor, but it requires a slow dose ramp-up to limit the risk of the potentially dangerous tumor lysis syndrome (TLS), where the cancer cells are killed too quickly for the body to handle. Unfortunately, a few patients have CLL that is moving so fast that the ramp-up may be too slow to catch up with their disease, and for all patients, the lengthy ramp-up and the associated need for frequent blood tests are an inconvenience.
Venetoclax also has been associated with low blood counts, especially the infection-fighting neutrophils, but also other cells, including red cells, all white cells, and platelets.
Lisaftoclax is a novel, oral BCL-2 inhibitor that is being studied to see if it is safe to use with a much quicker daily versus weekly ramp-up.
Method and Participants:
As is the case with all early-phase open-label studies, the purpose was to assess the safety and better understand and define the best dose.
- 45 patients were enrolled
- 42 pts experienced any-grade treatment-related adverse events including low neutrophils (55.6%); anemia (42.2%); decreased total white blood cell count (40%); low platelets (37.8%); high uric acid (31.1%); diarrhea (20%)
- 28 (62.2%) pts experienced grade more serious side effects
- Although not designed to study response, 41 patients were evaluated. There was 1 complete response (CR), and 27 achieved partial response (PR) for an objective overall response rate (ORR) of 68.29%.
- The go-forward dose of lisaftoclax as a single drug therapy was established as 600 mg.
It is much too early to predict how lisaftoclax will fit into the treatment paradigm for chronic lymphocytic leukemia/small lymphocytic lymphoma. Still, right now, it looks very similar to venetoclax, with the possible advantage of a faster ramp-up to the treatment dose. Whether it is more or less safe and as effective as venetoclax is unknowable at this point. However, even if it turns out to be a “me too” BCL-2 inhibitor, that would still be a significant benefit for those with CLL/SLL as it would offer another therapy choice.
Links and resources:
The ASCO 2022 abstract that gives more detailed details can be found by clicking here:
ASCO 2022: A phase Ib/II Study of Lisaftoclax a Novel BCL2 inhibitor in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (R/R CLL/SLL.
Here is a thorough review article on BCL-2 written by a CLL patient: A Look in the Treatment Toolkit – Bcl-2 Antagonists.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer, CLL Society, Inc.