Choosing a BTK Inhibitor and Fixed-Duration Strategy

Clinicians weighing frontline therapy for chronic lymphocytic leukemia (CLL) must choose both a Bruton tyrosine kinase (BTK) inhibitor and a treatment strategy. This segment reviews how acalabrutinib and zanubrutinib improved on ibrutinib with less atrial fibrillation, their subtle differences in headache, hypertension, and neutropenia, and the guideline positioning of newly available pirtobrutinib for frail or cardiac-comorbid patients. The faculty then compare fixed-duration options: venetoclax plus obinutuzumab, backed by long-term follow-up, and all-oral acalabrutinib plus venetoclax from the AMPLIFY trial, which appears to add no new toxicities and keeps atrial fibrillation very low. They explain why they apply the oral doublet broadly despite AMPLIFY excluding high-risk genomic features, citing relapsed-setting data and an unrestricted label. Infusion reactions with obinutuzumab, particularly in patients with high lymphocyte counts treated locally, favor the doublet, though dual oral agents may raise copays. Continuous single-agent therapy remains an option for select patients unable to attend monitoring.