Phase II Trial of Acalabrutinib in Ibrutinib-Intolerant Patients With CLL
Posted: Monday, September 16, 2019
A phase II trial presented at the 2019 American Society of Clinical Oncology Annual Meeting (Abstract 7530) and published in the Journal of Clinical Oncology suggests that continuing therapy with the Bruton’s tyrosine kinase inhibitor acalabrutinib in patients with chronic lymphocytic leukemia (CLL) who discontinued previous therapy may prove to be a viable strategy. Kerry Anne Rogers, MD, of The Ohio State University, and colleagues reported that acalabrutinib appears to be tolerable and active in patients with CLL who had adverse reactions to ibrutinib.
There were 60 patients recruited to this study; they had relapsed or refractory CLL and had discontinued ibrutinib therapy because of grade 3 or 4 adverse events or persistent grade 2 adverse events. Enrolled patients had progressive disease after discontinuation of ibrutinib. Patients were given 100 mg of acalabrutinib twice a day by mouth in 28-day cycles until their disease progressed or there were unacceptable adverse events.
The median number of prior therapies for these patients was two, and they were treated with ibrutinib for a median of 6 months. Adverse events that had led to the discontinuation of ibrutinib included atrial fibrillation/flutter (25%), diarrhea (12%), arthralgia (10%), and rash (12%).
After a median of 19 months on acalabrutinib, 67% of patients remained on the drug. The overall response rate was 77%, with 1 of 60 patients achieving a complete response and 42 of 60 achieving a partial response. The 21-month progression-free survival rate was 76%.
Treatment discontinuations were mostly due to progressive disease or adverse events such as pneumonia, diarrhea, headaches, ascites, arthralgia, and subdural hematoma. Other adverse events of any grade included diarrhea (48%), headache (40%), contusion (35%), and dizziness (32%). Grade 5 adverse events included pneumonia, bronchopulmonary aspergillosis, and ventricular fibrillation, but none were considered to be related to treatment.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.
