Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Preliminary data from this study suggests that patients with CLL who are on venetoclax plus obinutuzumab and reach undetectable measurable residual disease (uMRD) may be able to discontinue therapy early. MRD testing appears helpful in guiding decisions about treatment duration in patients with CLL.
Who Performed the Research and Where Was it Presented:
Dr. Meghan Thompson from Memorial Sloan Kettering Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2024.
Background:
Venetoclax is a BCL2 inhibitor that is usually used as a limited-duration therapy for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The suggested use is one year for frontline treatment and two years for relapsed / refractory CLL / SLL. However, researchers are interested in whether measurable residual disease testing could potentially be a better way of determining treatment duration rather than a one-size-fits-all approach. MRD testing measures the amount of CLL cells in the blood or bone marrow. These tests can detect extremely small numbers of cancer cells, ranging from 1 in 10,000 cells (1 x 10-4) to 1 in 1 million cells (1 x 10-6), depending on the type of test. UMRD status is associated with deeper remissions and longer progression-free survival. For this study, researchers used an MRD-guided approach to determine the duration of frontline treatment with venetoclax plus obinutuzumab.
Methods and Participants:
This was a phase 2 clinical trial of venetoclax plus obinutuzumab in patients with treatment-naïve CLL. The current treatment standard is 12 cycles (1 cycle = 28 days) of venetoclax. MRD testing was performed on peripheral blood samples using next-generation sequencing (1 x 10-6). If patients were MRD-negative at cycle 9, they stopped treatment and were monitored. MRD-positive patients continued on therapy. If patients were MRD-negative at cycle 12, they stopped treatment. If patients were MRD-positive at cycle 12, they continued on therapy for another year. Patients were monitored for clinical progression.
Results:
- One hundred patients enrolled in the trial, and the study is still ongoing. Some patients are still on active treatment, and some are just being monitored for signs of progression.
- Half (41/81) of the patients were uMRD at cycle 9 and were able to stop therapy.
- An additional 29 patients were uMRD at cycle 12 and were able to stop therapy.
- Three patients had detectable MRD at cycle 12 and continued on therapy through cycle 24.
- Thus far, progression-free survival 24 months after completing treatment was the same regardless of whether patients stopped therapy at cycle 9 or cycle 12.
- Follow-up is still ongoing as the primary endpoint for this study is 36-month progression-free survival.
Conclusions:
The preliminary data from this study suggests that patients with CLL who are on venetoclax plus obinutuzumab and reach uMRD may be able to discontinue therapy early without any significant changes in progression-free survival. MRD testing appears to be useful for guiding decisions about treatment duration in patients with CLL. While MRD testing is not yet part of regular clinical practice, it may be one day as many clinical trials incorporate it to guide treatment decisions. It holds the promise of limiting patients’ exposure to less medication if the CLL has quickly responded and extends its use or augment if not. At this time, MRD guidance is most likely more pertinent in treatments with already limited-duration therapies, such as the combination used in this study.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Minimal Residual Disease (MRD)-Adapted Duration of Frontline Venetoclax and Obinutuzumab Treatment for Fit Patients with Chronic Lymphocytic Leukemia (CLL)
