Authored by Brian Koffman, MDCM )retired), MSEd
Bottom Line:
The risk of a dangerous tumor lysis syndrome, when venetoclax is started, has limited its use in the community. A new trial looks for safer ways to start treatment.
Who Performed the Research:
Dr. Farrukh Awan of UT Southwestern Medical Center, Dallas, Texas, specializes in the care of CLL / SLL and related cancers. He shares the rationale and details of this ongoing trial.
Background:
Venetoclax’s ability to rapidly kill CLL cells is a double-edged sword as its rapid killing can lead to increased risks from high levels of potassium, uric acid, and other internal cellular chemicals that are spilled out into the bloodstream when the CLL cells are too quickly lysed (killed) for the kidneys to handle, resulting in tumor lysis syndrome (TLS). These dangerous chemical imbalances in the blood necessitate a slow ramp-up and close monitoring when venetoclax is started. The process is cumbersome and limits the accessibility to venetoclax-based therapies for chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL / SLL), especially outside of academic settings. This trial looks at different ways to reduce the risk of TLS and limit the need for frequent clinic visits for blood tests.
Trial Design:
There are four arms to this multi-centered trial for previously untreated CLL patients:
- Arm A: Patients receive oral venetoclax combined with IV obinutuzumab (Gazyva) with a five-week venetoclax ramp-up (standard of care).
- Arm B: Patients receive oral venetoclax with oral acalabrutinib, with a five-week venetoclax ramp-up.
- Arm C and Arm D: Patients will receive venetoclax in combination with oral acalabrutinib, with differing ramp-ups for venetoclax.
The study duration is approximately 28 months. The primary research outcome is measuring which arm best reduces TLS risk.
Summary and Discussion:
This is an important trial, especially given that three out of four participants will receive the all-oral combination of acalabrutinib and venetoclax, which is likely to be approved based on the AMPLIFY trial results. The other quarter will receive an excellent standard of care treatment of venetoclax and obinutuzumab. All arms of this trial are excellent options for frontline treatment of CLL. There will be more monitoring and close observation of the patients in this trial, but the results could significantly influence the future direction of CLL therapy.
Resources:
To learn about the trial or if you are interested in enrolling, please visit: A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL).
Enjoy Dr. Koffman’s interview with Dr. Awan here:
