The Bottom Line:
Adding venetoclax to ibrutinib in high-risk patients with chronic lymphocytic leukemia (CLL) who have been on ibrutinib for more than one year was very effective in helping patients reach undetectable measurable residual disease (uMRD). In addition, the side effects were manageable and typical of those seen with ibrutinib and venetoclax individually.
Who Performed the Research and Where Was it Presented:
Dr. Philip Thompson from MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Bruton’s tyrosine kinase (BTK) inhibitors have been wonderfully effective in treating CLL and small lymphocytic lymphoma (SLL). Still, they do not entirely remove all disease and thus must be taken indefinitely. Adding venetoclax may help patients get to uMRD, allowing them to stop therapy. However, previous studies that have looked at combining ibrutinib and venetoclax have usually excluded patients who have previously been treated with these agents, so it is unknown whether combining these agents in patients already on ibrutinib treatment would still be effective.
In this interview, Dr. Brian Koffman interviewed Dr. Philip Thompson, a physician in the CLL group at MD Anderson Cancer Center in Houston, TX. They discussed the results of a new study examining whether adding venetoclax to ibrutinib in patients already on ibrutinib would help improve their responses and reach uMRD.
Methods and Participants:
This is a phase 2 clinical trial of the addition of venetoclax in patients with high-risk genomic features who had been on ibrutinib for at least one year, regardless of whether it was their first or a later line of therapy. In addition, patients had to have detectable disease and still be responding to ibrutinib. High-risk was defined as the presence of at least one of the following: del(17p) or TP53 mutation; complex karyotype; del(11q); or elevated β2-microglobulin. Patients received venetoclax for a maximum of 2 years. After that, they could continue on ibrutinib or discontinue treatment if uMRD was achieved.
- A total of 45 patients were enrolled in the study, and 63% of patients had del(17p) and/or mutated TP53.
- Three out of four patients (73%) reached uMRD in the bone marrow.
- One in two patients (56%) improved their response from partial remission to complete remission.
- Ten patients stopped venetoclax early after reaching uMRD at two consecutive assessments (5 at month 12 and 5 at month 18).
- Five patients have progressed: 1 during combination therapy, three during ibrutinib maintenance, and one with Richter’s Syndrome during observation after achieving uMRD.
- Thus far, with approximately 12 months of follow-up after venetoclax treatment, 2 out of 3 patients remain MRD-negative.
- The most common overall side effect was diarrhea, which occurred in all patients and was mild to moderate. This was expected as diarrhea is very common with the combination of ibrutinib plus venetoclax.
- The most common severe side effect was low neutrophil counts in 20% of patients. Still, there were no low neutrophil counts with fever (which would indicate an infection).
- There were no cases of tumor lysis syndrome, which can sometimes be seen when starting on venetoclax.
- Five out of 45 patients had to stop ibrutinib because of cardiac side effects known to occur on ibrutinib.
Adding venetoclax to ibrutinib in high-risk patients who had been on ibrutinib for more than one year was very effective in helping patients reach uMRD. The side effects were manageable and typical of those with ibrutinib and venetoclax. Patients are still being monitored to determine the durability of the responses.
What is especially interesting in this trial is the protocol that minimized exposure to and, thus, the risks associated with taking two drugs. In addition, adding venetoclax to ibrutinib was purposed to reach uMRD and offer a limited-duration therapy.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Venetoclax Consolidation Achieves Durable Off-Treatment Remissions in Patients with High Risk CLL Who Have Been on Ibrutinib More Than a Year
Take care of yourself first.
Ann Liu, PhD