Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Patients with CLL who have been treated with fixed-duration venetoclax-based regimens can later be retreated with venetoclax-based therapies.
Who Performed the Research and Where Was it Presented:
Dr. Mazyar Shadman from the Fred Hutch Cancer Center and colleagues presented the results at the 2025 American Society for Hematology (ASH) Annual Meeting.
Background:
Venetoclax is a BCL2 inhibitor that is approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is usually given as a fixed-duration treatment, often in combination with other therapies such as anti-CD20 monoclonal antibodies (obinutuzumab, rituximab). Additionally, the combination of venetoclax and acalabrutinib recently received FDA approval for use as a first-line treatment for CLL / SLL. Because venetoclax-based therapies are potent and commonly only given for a limited amount of time, researchers wanted to know whether patients could be retreated with venetoclax at a later date when their disease progresses.
Methods and Participants:
This retrospective study used anonymized electronic health record data from the Optum Market Clarity database. It included patients with CLL who were treated with a venetoclax-based regimen and then were treated with a second venetoclax-based regimen in a later line of therapy.
Results:
- A total of 48 patients with CLL who were retreated with venetoclax were included in the study.
- 68% of patients had received a BTK inhibitor before being treated with venetoclax for the first time.
- The median duration of first venetoclax treatment was 12 months.
- For their first venetoclax-based treatment, a surprisingly high percentage of patients received venetoclax as monotherapy (58%). It was combined with obinutuzumab or rituximab in 33%, or with a BTK inhibitor 8%.
- The median time between the end of the first venetoclax treatment and the beginning of the second venetoclax treatment was 21 months.
- 85% of patients had no treatment between the two venetoclax treatments.
- An identical again surprisingly high 58% of patient received venetoclax monotherapy as their venetoclax retreatment, as they received it first line.
- After any venetoclax retreatment, the median time to next treatment was 26 months. To be clear, this was calculated from the initiation of the therapy, so it included all the time on treatment.
- Only 27% were given venetolclax second line in combination with either rituximab or obinutuzumab, which would be more in line with guidelines. For this smaller group, the time to the next treatment had not reached at the time of publication. While the time on treatment is not stated in the abstract, second-line venetoclax is approved for 24 months in combination with rituximab.
Conclusions:
This study showed that patients with CLL who have been treated with fixed-duration venetoclax-based regimens can later be successfully retreated with venetoclax-based therapies. Patients retreated with venetoclax-based regimens were in remission for more than two years before needing another treatment. The numbers are too small, and the data are too immature to analyze, but if the early trend continues, later results should show even longer responses when veneoclax is combined with an anti-CD20 monoclonal antibody such as rituximab or obinutuzumab. These results are really good news for patients, because it shows that venetoclax is still an effective therapy even when given a second time around.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Venetoclax retreatment of real-world patients with chronic lymphocytic leukemia previously treated with venetoclax-based regimens
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