Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Fixed-duration therapy using venetoclax-based combinations is just as effective as continuous BTK inhibitor therapy for first-line treatment of CLL.
Who Performed the Research and Where Was it Presented:
Othman Al-Sawaf from University Hospital of Cologne and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Currently, there are two main approaches for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) with targeted therapies. Patients may receive either 1) continuous treatment with a BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib) or 2) fixed-duration treatment with a combination of targeted therapies, which usually includes a BCL2 inhibitor such as venetoclax. While both these approaches have shown to be superior to chemoimmunotherapy, they have not been directly compared to each other before.
Methods and Participants:
CLL17 is an international, randomized, phase 3 clinical trial for patients with previously untreated CLL comparing three different treatments.
- Continous ibrutinib
- Fixed-duration venetoclax plus obinutzumab
- Fixed-duration venetoclax plus ibrutinib
Both fixed-duration treatments were given for approximately one year. The primary outcome was progression-free survival (the amount of time until the disease gets worse). This is the first reported head-to-head comparison of these three therapies.
Results:
- A total of 909 patients were randomized to treatment, and the median follow-up time was 34 months (just under three years).
- Both fixed-duration treatments were just as effective as continuous ibrutinib, with approximately 80% of patients in each group being progression-free after three years.
- For patients with unmutated IGHV, three-year progression-free survival was similar among all treatment groups (75-80%).
- For patients with higher risk mutations, such as deletion 17p or TP53 mutation, progression-free survival was slightly lower with fixed-duration treatments compared with continuous ibrutinib, but more follow-up is needed to determine whether this is a significant effect.
- Overall survival (how many patients were alive) after three years was very high in all groups (91-96%).
- Cardiovascular side effects were more common in the group receiving continuous ibrutinib (35%).
- Severe infections were more common in the combination therapy groups, particularly the venetoclax plus obinutuzumab group.
Conclusions:
This study provides excellent news for patients with CLL / SLL. Fixed-duration treatment with venetoclax plus obinutuzumab or venetoclax plus ibrutinib was equally as effective as continuous treatment with ibrutinib for patients with CLL. The results were true even in higher-risk patients with unmutated IGHV. This new finding is in contrast to prior indirect comparisons. Fixed-duration treatments can be appealing because they allow patients to take a break from the burdens of being on active therapy (time, money, side effects) and may lower the risk of developing mutations that lead to resistance. This study gives both patients and health care providers reassurance that there are no major differences in efficacy between the two approaches. This study also shows that patients with CLL have an excellent prognosis when they are treated with targeted therapies (fixed-duration or continuous) with very high overall survival rates at three years. CLL Society looks forward to learning more about the long-term outcomes as this study continues to follow patients.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial
A full paper was also published in the New England Journal of Medicine, which can be found here, though it is paywalled: Fixed-Duration versus Continuous Treatment for Chronic Lymphocytic Leukemia
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