Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
An ongoing phase 2 clinical trial is evaluating the efficacy and tolerability of fixed-duration zanubrutinib plus venetoclax for relapsed / refractory CLL. Early clinical activity and safety data are promising thus far.
Who Performed the Research and Where Was it Presented:
Dr. Inhye Ahn from Dana-Farber Cancer Institute and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Bruton tyrosine kinase (BTK) inhibitor zanubrutinib and B-cell lymphoma 2 (BCL2) inhibitor venetoclax are two effective treatments for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). While venetoclax has traditionally been combined with the anti-CD20 monoclonal antibody rituximab, results from clinical trials have shown that combining zanubrutinib with venetoclax is highly effective as a first-line treatment for CLL / SLL. Zanubrutinib plus venetoclax is an all-oral combination that does not require IV infusions (which is how rituximab is administered). For this study, researchers wanted to know if fixed-duration zanubrutinib-venetoclax was effective specifically for patients with relapsed / refractory CLL, who tend to be harder to treat.
Methods and Participants:
This is a phase 2 clinical trial of zanubrutinib-venetoclax in patients with relapsed / refractory CLL. Zanubrutinib-venetoclax was given for a fixed duration of 15 cycles, with zanubrutinib starting one cycle before venetoclax ramp-up. The primary endpoint is undetectable measurable residual disease in the bone marrow.
Results:
- This study is ongoing, and 26 out of 45 patients have been enrolled.
- The majority of side effects have been mild and within the expected frequency ranges that are known to occur with use of these drugs.
- The most common side effects were bruising (57%), diarrhea (42%), low platelet counts (38%), and low neutrophil counts (35%).
- Two patients developed atrial fibrillation (abnormal heart rhythm).
- No tumor lysis syndrome was observed.
- While final efficacy data are not yet available, midway through the study, 95% of patients have responded to treatment thus far.
Conclusions:
Thus far, fixed-duration zanubrutinib-venetoclax seems to be well-tolerated, and the initial response data are promising. The study is still recruiting patients, particularly those who have progressed on a previous covalent BTK inhibitor (ibrutinib or acalabrutinib). More information about the study can be found here: Zanubrutinib and Venetoclax in CLL (ZANU-VEN).
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: A Phase 2 Study of Zanubrutinib and Venetoclax (ZV) in Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)
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