Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Real-world data show that venetoclax-based therapy is associated with better outcomes in older patients with CLL compared with covalent BTK inhibitors.
Who Performed the Research and Where Was it Presented:
Dr. Scott Huntington from Yale University and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Many new drugs for chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) have shown great efficacy and safety in clinical trials, including covalent Bruton tyrosine kinase inhibitors (BTKi: ibrutinib, acalabrutinib, zanubrutinib) and BCL2 inhibitors (venetoclax). However, in the real world, outcomes often differ from those seen in clinical trials, possibly because people who enroll in trials tend to be healthier, live closer to research institutions, and are better educated. For instance, real-world studies have shown that patients on covalent BTKi more often discontinue early due to unacceptable side effects. This effect suggests that fixed-duration (e.g., 1-year) treatments that provide a defined endpoint might allow side effects to be tolerated and treatment to be sustained. This study compared real-world outcomes in patients with CLL treated with either continuous covalent BTKi or time-limited venetoclax-based regimens.
Methods and Participants:
This retrospective study used national Medicare claim data. It included elderly patients with CLL who started treatment for CLL between 2019 and 2022. Treatments were categorized as:
- Venetoclax-based
- Covalent BTKi
- Other – includes anti-CD20 monoclonal antibodies (rituximab, obinutuzumab), chemoimmunotherapy
Unlike a randomized control trial that ensures balance in each cohort, real-world data takes all comers.
Results:
- A total of 10,949 patients were included.
- 14% of patients received venetoclax-based therapies
- 55% received covalent BTKi
- 32% received other therapies
- The average patient age was 77 years, with half followed for more than two years.
- Statistically modeled three-year overall survival (how many patients were alive) was higher in the venetoclax group (77%) than in patients treated with the covalent BTKi (67%) or other therapies (62%).
- Using statistical modeling, more patients in the venetoclax group did not need another line of therapy at three years (86%) compared with covalent BTKi (69%) and other therapies (52%).
Conclusions:
Real-world data shows that venetoclax-based therapy was associated with better outcomes in older Medicare patients with CLL compared with covalent BTKi. This result was somewhat surprising because CLL17, a phase 3 clinical trial, showed that fixed-duration venetoclax-based treatment and continuous ibrutinib had equally good outcomes. Unfortunately, the abstract does not tell us about the makeup of the groups. Maybe the Medicare patients who were prescribed BTKi were at higher risk due to frailty, as it is less intense therapy. Alternatively, those prescribed BTKis may have been at higher risk due to genetic markers, del17p, or mutated TP53. We also do not know how many in each group were able to stay on their initial therapy. This research is reassuring because both venetoclax-based therapy and BTKis were shown highly effective in a non-research older Medicare population.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Real-world overall survival and time to next treatment among elderly United States Medicare beneficiaries with chronic lymphocytic leukemia in the front-line setting
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