The Bottom Line:
The combination of ibrutinib plus venetoclax is an effective first-line treatment for high-risk chronic lymphocytic leukemia (CLL). In this trial, nearly 2 in 3 patients achieve undetectable minimal residual disease (uMRD). The results seen here are very similar to those from several other trials testing the combination of ibrutinib plus venetoclax as a first-line treatment.
Who Performed the Research and Where Was it Presented:
Dr. Bill Wierda from MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Background:
Most of the CLL and small lymphocytic lymphoma (SLL) research is currently looking at combination therapies that combine 2 or 3 drugs (doublets or triplets) with different mechanisms of action. The hope is that hitting the cancer harder will get patients to undetectable measurable residual disease (uMRD) faster, where no CLL/SLL cells can be detected, and limit the time patients need to take drugs. Getting to uMRD has also been linked with more prolonged progression-free survival. Right now, one of the most studied combinations is the BTK inhibitor ibrutinib plus the BCL2 inhibitor venetoclax.
In this video, Dr. Matthew Davids, Director of the Center for Chronic Lymphocytic Leukemia (CLL) at Dana-Farber Cancer Institute, interviewed Dr. Bill Wierda, a Professor of Medicine in the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas. They discussed updated results from a phase 2 clinical trial of a combination of ibrutinib plus venetoclax as a first-line treatment.
Methods and Participants:
This phase 2 clinical trial looked at the efficacy of ibrutinib plus venetoclax in high-risk patients with previously untreated CLL. High-risk features included: del(17p), mutated TP53, del(11q), unmutated IGHV, or age ≥65 years. Patients received a combination of ibrutinib plus venetoclax for two years. The protocol was later amended to allow for one additional year of combination therapy for patients still MRD-positive after two years.
Results:
- The initial results from this trial with 80 patients have previously been published here.
- These newly updated results include data from 120 patients with a median follow-up of 4 years.
- The best response rate (meaning that a patient reached uMRD at any point in the study) was 72%.
- At year 2, 64% of patients were MRD-negative, and most opted to discontinue therapy.
- Among patients who were MRD-positive at year two and received an additional year of therapy, 63% converted to MRD-negative.
- More patients with unmutated IGHV reached uMRD status than patients with mutated IGHV.
- Thus far, there have been very few MRD relapses (meaning they went from undetectable to detectable MRD).
- Of the 11 patients who experienced MRD relapse, ten are being monitored without any active therapy for CLL and without clinical disease progression.
- Patients who experienced MRD relapse tended to be the slowest to respond to the treatment.
- The 4-year progression-free survival was 95%, and the 4-year overall survival was 97%.
Conclusions:
The combination of ibrutinib plus venetoclax is effective as a first-line treatment for high-risk CLL/SLL, with nearly 2 in 3 patients achieving undetectable minimal residual disease (uMRD) in this trial. The results seen here are very similar to those from several other trials testing the combination of ibrutinib plus venetoclax as a first-line treatment (GLOW and CAPTIVATE and FLAIR). This combination has already been approved in the European Union, and we are awaiting Canadian approval, but it is unlikely to be approved in the USA. Both drugs are already FDA approved for use as monotherapies and could be used together “off-label” if the patient and doctor agree that it is the best option.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Combined Ibrutinib and Venetoclax for First-Line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL): 4-Year Follow-up Data
Take care of yourself first.
Ann Liu, PhD
