In earlier stage clinical studies, acalabrutinib has shown promise as a potent Bruton’s tyrosine kinase inhibitor with minimal off-target activity. At the ASH 2018 Annual Meeting, researchers presented an updated analysis of the safety and efficacy results from the ACE-CL-001 study.
Eligible patients had previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma that met International Workshop on Chronic Lymphocytic Leukemia criteria for treatment, had European Cooperative Oncology Group performance status of ≤2, and declined or were not appropriate candidates for chemoimmunotherapy. Patients received oral acalabrutinib (100 mg twice daily or 200 mg daily) until progressive disease or unacceptable toxicity. The primary end point was safety, and secondary end points included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). A total of 99 patients were treated, with a median age of 64 years. The median study duration was 42 months, with 89% of patients remaining on the study treatment.
In terms of safety, the most common adverse events (all grades) were diarrhea (49%), headache (44%), upper respiratory tract infection (40%), contusion (39%), arthralgia (33%), weight increase (31%), nausea (30%), and cough (23%). Serious adverse events occurred in 35 patients, and included pneumonia (n = 4), influenza (n = 3), sepsis (n = 2), and sinusitis (n = 2). Grade 3/4 atrial fibrillation occurred in 2 patients and grade 3/4 bleeding events occurred in 3 patients. Hypertension occurred in 17 patients, in 7 of whom it was grade 3; there were no grade 4 hypertension events. Infections occurred in 82 patients, in 14 of whom they were grade 3 or 4.
ORR was 97%, and the median DOR, defined as partial response or better, was not reached. The 36-month DOR and PFS rates were 98% and 97%, respectively. For the 5 patients who achieved complete response (CR), the median time to CR was 28 months. Researchers concluded that acalabrutinib monotherapy produced high response rates and demonstrated an acceptable safety profile in patients with previously untreated CLL, and clinical studies continue.
Byrd JC, et al. ASH 2018. Abstract 692.