Medically reviewed by Dr. Brian Koffman
The Bottom Line:
A combination of ibrutinib plus venetoclax is a very effective first-line treatment for CLL, and 90% of patients are progression-free after five years. Retreatment with ibrutinib or acalabrutinib was effective for patients who experienced disease relapse.
Who Performed the Research and Where Was it Presented:
Dr. Nitin Jain from MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2023.
Background:
Combination therapies have become a very active area of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) research. The idea is that using multiple targeted therapies with different mechanisms of action will get patients into deeper remissions. These combination therapies may also be limited in duration, meaning patients can take a break from treatment once they are in remission. In this interview, Dr. Jain provides an update with 5-year follow-up data from a phase 2 clinical trial of ibrutinib plus venetoclax as a first-line therapy for CLL.
Methods and Participants:
This is a phase 2 clinical trial of a combination of ibrutinib plus venetoclax for first-line treatment of CLL. All patients had previously untreated CLL and at least one high-risk feature: del(17p), mutated TP53, del(11q), unmutated IGHV, or age ≥65 years. Patients received a combination of ibrutinib plus venetoclax for two years, with the option to extend treatment if they had not reached undetectable measurable residual disease (uMRD) by year 2.
Results:
- A total of 120 patients were enrolled between 2016 and 2019.
- With a median follow-up of a little over five years, 72% of patients had uMRD in the bone marrow at some point during the study.
- After five years, 90% of patients have not had disease progression (progression-free survival), and 95% are still alive (overall survival).
- Only eight patients had their disease progress; one during active treatment and seven after therapy had stopped.
- Of patients with disease progression, five have required retreatment, and they received ibrutinib, acalabrutinib, or acalabrutinib plus venetoclax. All patients responded to retreatment.
- Side effects were typical of what has been seen with ibrutinib and venetoclax individually. Low white blood cell counts were common, and there were cases of atrial fibrillation.
Conclusions:
The combination of ibrutinib plus venetoclax is a very effective first-line treatment for CLL, and 90% of patients are progression-free after five years. Retreatment with ibrutinib or acalabrutinib was effective for patients who experienced disease relapse. Ibrutinib plus venetoclax is a very attractive combination because it is a time-limited treatment, and both drugs can be taken orally. However, this combination has not received approval from the FDA, although it has been approved in other countries and can be used off-label in the US.
Additionally, clinicians have been moving towards using second-generation BTK inhibitors such as acalabrutinib and zanubrutinib, which are safer than ibrutinib. Currently, combinations of acalabrutinib plus venetoclax and zanubrutinib plus venetoclax are being tested in phase 3 clinical trials, and FDA approval is likely to depend on the results of these trials. We hope these combinations will be just as effective as ibrutinib plus venetoclax, and we eagerly await the results of these trials.
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): 5-Year Follow-up Data
Take care of yourself first.
Ann Liu, PhD
