This phase 2 trial evaluated acalabrutinib, a highly selective, covalent, Bruton’s tyrosine kinase (BTK) inhibitor in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who are intolerant of ibrutinib. Eligible patients had ≥1 prior therapies for CLL and had discontinued ibrutinib due to grade 3 or 4 adverse events or persistent or recurrent grade 2 adverse events, and who had progressive disease after ibrutinib discontinuation.
Patients received a twice-daily, oral, 100-mg dose of acalabrutinib in 28-day cycles until disease progression or unacceptable toxicity. The primary end point was overall response rate. A total of 60 patients with a median age of 70 years were treated. Patient characteristics included bulky disease ≥5 cm (32%), Rai stage III or IV disease (52%), del17p (28%), del11q (23%), and unmutated IGHV (79%). Patients had received a median of 2 prior therapies, and the median duration of prior ibrutinib therapy was 6 months. The most common adverse events that led to ibrutinib discontinuation were atrial fibrillation/flutter (28%), diarrhea (12%), rash (12%), and arthralgia (10%).
At a median follow-up of 23 months, 62% of patients continued to receive acalabrutinib. Serious adverse events of any grade occurred in 21 patients (35%); the most common adverse events were pneumonia (10%) and neutropenia (8%). The majority of discontinuations were due to progressive disease (15%) and adverse events (12%), including 2 patients with pneumonia and 1 patient each with diarrhea, headache, endometrial cancer, arthralgia, and subdural hematoma. Grade 1 or 2 atrial fibrillation occurred in 3 patients, and major hemorrhage occurred in 2 patients. There were 4 deaths due to pneumonia (N = 2), bronchopulmonary aspergillosis (N = 1), and ventricular fibrillation (N = 1), respectively, but none were considered to be related to treatment.
In terms of efficacy, investigator-assessed overall response rate was 72%, with a 5% complete response rate. The 18-month progression-free survival rate was 73.5%. Researchers concluded that acalabrutinib is tolerable and effective in patients intolerant of ibrutinib, representing a potential strategy to continue BTK inhibitor therapy in this patient population.
Abstract 7530; Rogers KA, et al.