Acalabrutinib (Calquence) is a next-generation targeted oral drug that blocks the action of Bruton tyrosine kinase, an enzyme that plays a key role in the growth of cancer cells. Acalabrutinib was approved by the FDA for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) based on 2 large clinical studies, known as ELEVATE-TN and ASCEND. Both studies compared acalabrutinib with standard therapies for CLL.
Results from a third clinical trial called ACE-CL-001, which were presented during the ASCO 2020 Virtual Scientific Program, provided updated safety and efficacy data for acalabrutinib in the first-line treatment of patients with CLL.1 Adults with CLL/SLL could enroll in ACE-CL-001 if they met specific criteria for CLL/SLL treatment and were not eligible for or refused to receive standard chemotherapy. Treatment consisted of acalabrutinib (100 mg twice daily or 200 mg once daily, later switched to 100 mg twice daily) until disease progression or until side effects became unacceptable. Measures of the efficacy of acalabrutinib included rate of response, duration of response, and time to response.
The ACE-CL-001 study included 99 patients with CLL: 62 received acalabrutinib at a dose of 100 mg by mouth twice daily and 37 received acalabrutinib at a dose of 200 mg by mouth once daily. The median age of patients was 64 years, and approximately half (47%) of the patients had advanced-stage CLL/SLL.
After more than 4 years of follow-up, 86% of patients who started on acalabrutinib remain on treatment, and 9 patients stopped taking acalabrutinib because of side effects (N = 6) or disease progression (N = 3).
The most common side effects associated with acalabrutinib therapy were diarrhea (52%), headache (45%), upper respiratory infection (44%), muscle pain (42%), and bruising (42%). Other side effects included severe infection (15%), severe bleeding events (3%), and severe hypertension (11%). Atrial fibrillation occurred in 5% of patients. Secondary cancer diagnoses, excluding nonmelanoma skin cancer, occurred in 11% of patients.
Almost all (97%) of the patients who received acalabrutinib responded to it: 7% had a complete response and 90% had a partial response. The median time to response was 3.7 months. Rates of response were similar among patients with CLL/SLL, including those with high-risk disease.
The median duration of response has not yet been reached in this trial; however, after 4 years of treatment, 97% of patients who had responded to acalabrutinib were still responding. The researchers concluded that long-term data from the ACE-CL-001 trial support first-line use of acalabrutinib in patients with CLL/SLL.
Reference
- Byrd JC, Woyach JA, Furman RR, et al. Acalabrutinib in treatment-naïve chronic lymphocytic leukemia: mature results from phase II study demonstrating durable remissions and long-term tolerability. J Clin Oncol. 2020;38(15_suppl). Abstract 8024.
