Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Second-line targeted therapies are very effective for patients with CLL who relapse after first-line, fixed-duration venetoclax-based therapy.
Who Performed the Research and Where Was it Presented:
Dr. Carsten Niemann from the University of Copenhagen and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Targeted therapies such as BTK inhibitors and BCL2 inhibitors have revolutionized the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Most patients now receive first-line treatment with a continuous BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib) or a fixed-duration venetoclax-based combination therapy. While these treatments can provide long remissions, they are not curative, and eventually patients may relapse. Researchers sought information on which second-line therapies might be most effective in patients who had previously received first-line treatment with a venetoclax-based therapy.
Methods and Participants:
The GAIA / CLL13 trial enrolled 926 physically fit patients with CLL and randomly assigned them to one of four treatment groups.
- Chemoimmunotherapy (CIT)
- Venetoclax plus rituximab (VR)
- Venetoclax plus obinutuzumab (VO)
- Ventoclax plus obinutuzumab plus ibrutinib (VOI)
Researchers followed these patients over time, and this study gathered data on patients who had their disease progress to the point where they needed a second-line treatment. Second-line treatments were chosen by the treating physician.
Results:
- A total of 177 patients received second-line therapy.
- 112 of these patients had received a venetoclax-based first-line treatment (VR, VO, or VOI), and their second-line treatments fell into the following categories:
- BTK-inhibitor-based (n=57)
- Venetoclax-based (n=23)
- Venetoclax plus BTK inhibitor (n=26)
- Chemoimmunotherapy (n=6)
- Treatment-free survival rates 2 years after starting second-line therapy were:
- BTK inhibitor-based: 78%
- Venetoclax-based: 81%
- Venetoclax plus a BTK inhibitor: 100%
- Chemoimmunotherapy: 28%
- Two-year overall survival rates were >90% in patients receiving second-line treatment with targeted therapies (BTK inhibitor-based, venetoclax-based, or venetoclax plus BTK inhibitor).
Conclusions:
Data have been sparse on outcomes for second-line therapies to help guide the appropriate sequencing of treatments. The importance of this study is that it demonstrates that venetoclax-based therapies and BTK inhibitor-based therapies are effective second-line treatments for patients who have already been treated with fixed-duration venetoclax-based therapies. This is great news for patients, because we just learned that fixed-duration venetoclax-based therapies are just as effective as continuous BTK inhibitor therapy as a first-line treatment. Now this study provides reassurance that there are good second-line options if patients relapse after a fixed-duration treatment, and they can even be re-treated with venetoclax-based combination therapies.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Efficacy of 2nd-line treatment in CLL after venetoclax-based 1st-line treatment: Results from the GAIA/CLL13 trial
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