Clinical Practice Insights: Comparing the Safety Profiles of Acalabrutinib, Ibrutinib, and Zanubrutinib
August 13th 2025
Panelists discuss how CLL treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects including cardiovascular events, hypertension, bleeding, diarrhea, and rash that typically occur early in treatment, noting that while second-generation BTKis may have slightly improved tolerability profiles compared with ibrutinib, most annoying adverse effects like arthralgias, cramps, and fatigue develop tachyphylaxis over time, with bleeding complications and late-onset dyskinesias being among the most challenging adverse events to manage across all BTKis.