The Bottom Line:
Final data from a phase 1/2 clinical trial with six years of follow-up show that first-line acalabrutinib produces high response rates and rapid, durable responses in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) regardless of high-risk genomic features. Acalabrutinib was well-tolerated, with a low incidence of atrial fibrillation and no new long-term safety issues identified.
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.
Acalabrutinib is a next-generation, covalent Bruton tyrosine kinase (BTK) inhibitor that received FDA approval in 2019 for treating CLL and SLL. Because BTK inhibitors must be taken continuously, the risk of developing some side effects increases over time. Therefore, long-term follow-up data are vital for assessing tolerability. However, previous analyses have shown that first-line treatment with acalabrutinib produced durable responses and good long-term tolerability.
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 the final results of a phase 1/2 trial of acalabrutinib as a first-line therapy for CLL / SLL with six years of follow-up.
Methods and Participants:
This was a phase 1/2 clinical trial of acalabrutinib as a first-line therapy in patients with previously untreated CLL / SLL. Patients received acalabrutinib twice daily until disease progression or unacceptable toxicity.
- While the initial results have previously been published here, Dr. Wierda and colleagues presented the final data with six years of follow-up.
- Ninety-nine patients were treated, and 71% were still on acalabrutinib at the final data cut-off. Adverse events (10%) and progressive disease (6%) were the most common reasons for discontinuation.
- The overall response rate was 97% (meaning patients experienced either partial or complete remission).
- Like ibrutinib, most patients (88%) experienced partial remission where the disease was reduced, but it was not completely eliminated.
- The average time to respond to treatment was about four months.
- After six years of follow-up, 90% of patients respond to treatment, and 87% are progression-free.
- The overall response rate was 100% in high-risk groups, including del(17p), del(11q), unmutated IGHV, and complex karyotype.
- Atrial fibrillation (abnormal heart rhythm) is a known side effect of BTK inhibitors. However, in this trial, it occurred in 6% of patients, which is lower than what has been seen with ibrutinib.
- High blood pressure occurred in 29% of patients.
- Bleeding and bruising occurred in 74% of patients but were mostly mild, with only 7% of cases being severe.
- Patients did experience more headaches with acalabrutinib, but these symptoms were typically mild and transient.
First-line treatment with acalabrutinib produced high response rates and rapid, durable responses in patients with CLL / SLL regardless of high-risk genomic features. In addition, Acalabrutinib was well-tolerated, with a low incidence of atrial fibrillation and no new long-term safety issues identified. Also, as reported in our previous coverage, acalabrutinib is equally as effective as ibrutinib but with fewer side effects.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Final Results of the Phase 1/2 Study of Acalabrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia with >6 Years of Follow-up
Take care of yourself first.
Ann Liu, PhD