Authored by Brian Koffman, MDCM )retired), MSEd
Bottom Line:
MRD-guided venetoclax-based therapy can lead to durable remissions in both the frontline and relapsed/refractory (R/R) setting in CLL.
Who Performed the Research and Where Was it Presented:
Leora Boussi led an international group of researchers to present the abstract: USING MINIMAL RESIDUAL DISEASE STATUS TO GUIDE VENETOCLAX TREATMENT DURATION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: INTERIM RESULTS FROM THE PHASE II VENETOSTOP STUDY in Milan, Italy, June 2025 at the European Hematology Association Annual Congress.
Background:
Venetoclax is a proven treatment for chronic lymphocytic leukemia (CLL). Studies show that patients who achieve undetectable measurable or minimal residual disease (uMRD) at the end of venetoclax therapy tend to have prolonged remissions and live longer. Monitoring for uMRD and using the results to inform when the best time is to stop venetoclax-based therapy may help doctors shorten treatment duration, reduce side effects, and lower the risk of drug resistance.
Methods:
This ongoing clinical trial is studying whether patients with CLL who reach undetectable MRD after at least six months of venetoclax can safely stop treatment early. A sensitivity of <10-5 (one CLL cell in 100,000) was used to define undetectable MRD. If patients meet specific uMRD-5 criteria, they stop venetoclax and are closely monitored with regular blood tests. The goal is to see how many can stay off treatment for at least one year without their disease returning. Patients whose disease comes back can restart venetoclax.
Results:
- Median age was 67 years, 82% male, 89% White, 5% Black, and 6% other or unknown race.
- 66 patients with CLL who had reached uMRD levels stopped venetoclax and entered a monitoring phase without treatment.
- 45 pts (68%) received first-line venetoclax, and 21 (32%) received venetoclax in the R/R setting. Venetoclax regimens included: monotherapy (n=4, 6%), venetoclax plus obinutuzumab (n=55, 83%), venetoclax plus rituximab (n=7, 11%). Median venetoclax duration prior to discontinuation was 10.1 months (range 6.2-22).
- After stopping treatment:
- 71% still had undetectable disease after 12 months off treatment.
- 46% still had undetectable disease after 24 months.
- The estimated progression-free survival was 97% at 12 months and 84% at 24 months.
- Six patients whose disease returned restarted venetoclax, and most responded again.
Conclusions:
This study is testing whether personalized treatment duration, specifically stopping venetoclax-based therapies based on MRD results, can help patients safely reduce time on the drug, reduce side effects, and avoid overtreatment. These very early data are promising.
The trial is ongoing, and future results will show how well this strategy allows patients to stay treatment-free while maintaining good disease control.
Other research, such as the FLAIR trial, is exploring extending treatment of venetoclax and ibrutinib until uMRD is reached and then doubling that time in the hopes of tailoring treatment duration in a way that leads to extremely durable remissions.
Using MRD to individualize treatment time makes good sense, but it can add considerable complexity to the disease management. Whether its use becomes common outside of clinical trials and academic centers is far from certain. Trials like this may help answer this and other questions about the role of MRD testing in personalizing CLL care.
Sources:
The actual EHA abstract with more details and graphs can be accessed at USING MINIMAL RESIDUAL DISEASE STATUS TO GUIDE VENETOCLAX TREATMENT DURATION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: INTERIM RESULTS FROM THE PHASE II VENETOSTOP STUDY
