The Bottom Line:
An ongoing phase 2 clinical trial is testing whether adding venetoclax to first-line BTK inhibitor therapy can deepen remissions for CLL patients.
Who Performed the Research and Where Was it Presented:
Dr. John Burke from Rocky Mountain Cancer Centers and colleagues are conducting the study, and the trial design is described in the journal Blood.
Background:
Bruton tyrosine kinase inhibitors (BTKi) are very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Still, they must be taken continuously, usually until disease progression or development of intolerable side effects. Over time, continuous use can lead to increased risk of unwanted side effects and / or acquired resistance. Also, when they are used as a single agent, BTKi are unlikely to produce deep remissions with undetectable measurable residual disease (uMRD).
B-cell lymphoma 2 inhibitor (BCL2i) venetoclax can be combined with other drugs to produce deep remissions with high rates of uMRD. The purpose of this study is to see if adding venetoclax to the treatment regimen of patients already on first-line covalent BTKi therapy can produce deep remissions with uMRD that allow for time-limited therapy.
Methods and Participants:
- This is a phase 2 clinical trial looking at whether adding venetoclax to first-line covalent BTKi therapy produces deep remissions with uMRD.
- To be eligible, patients must be currently receiving first-line treatment with a covalent BTKi (ibrutinib, acalabrutinib, zanubrutinib) and have been on therapy for at least six months.
- Patients will receive venetoclax for one year, and then they will be followed for an additional year.
- The primary endpoint is uMRD in the peripheral blood at the end of combination therapy.
- Other outcomes that will be assessed include response rates, duration of response, progression-free survival, and overall survival.
- Patients who reach uMRD will discontinue both venetoclax and covalent BTKi.
- Patients who still have detectable MRD will continue on covalent BTKi.
Conclusions:
We are fortunate to have several good therapies available to treat CLL / SLL. Studies like this are essential for helping us learn about how to sequence and combine therapies to help patients maximize the benefits of their treatments. If you are interested in participating in this study, more information can be found here: A Study to Evaluate the Effect of Venetoclax on Participants Receiving a Covalent Bruton’s Tyrosine Kinase Inhibitor (cBTKi) for First-line Chronic Lymphocytic Leukemia (1L CLL) to Achieve Deep Durable Remissions to Allow Off-treatment Period. (BRAVE).
Links and Resources:
Watch the interview on the abstract here:
You can read the actual abstract here: BRAVE: A Phase 2 Trial Evaluating the Efficacy and Safety of Venetoclax in Combination with Bruton’s Tyrosine Kinase Inhibitors in Patients with First-Line Chronic Lymphocytic Leukemia.
