My Treatment Approach: Shared Decision-Making in CLL: Balancing Safety, Efficacy, and Patient Preference in CLL - Episode 5
Clinical Practice Insights: Comparing the Safety Profiles of Acalabrutinib, Ibrutinib, and Zanubrutinib
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.
This segment provides clinical practice insights comparing the safety profiles of the 3 main Bruton tyrosine kinase inhibitors (BTKis): acalabrutinib, ibrutinib, and zanubrutinib. The experts discuss their real-world experience beyond clinical trial data, noting that while head-to-head studies show statistical differences in certain adverse events like atrial fibrillation, the practical clinical differences may be more nuanced. One expert emphasizes having the most extensive experience with ibrutinib due to its earlier approval in 2014, followed by acalabrutinib, and least experience with zanubrutinib as the most recent addition to the chronic lymphocytic leukemia (CLL) treatment landscape.
The discussion reveals that certain “annoying but rarely showstopping” adverse effects appear more commonly with ibrutinib, including arthralgias, rash, and muscle cramps affecting hands and feet. However, a crucial clinical insight is that patients typically develop tachyphylaxis to these minor adverse events, meaning the symptoms improve over time. This reassurance is important for patient counseling, as many patients worry about tolerating these adverse effects long term on continuous therapy. The experts emphasize that most of these annoying symptoms subside with time, and proper patient education about this expectation significantly helps with treatment adherence.
The most challenging adverse events to manage across all BTKis include chronic bleeding issues, particularly in elderly patients who may already be on anticoagulation or antiplatelet therapy. These patients develop fragile skin, easy bruising, and persistent bleeding that can be problematic regardless of which BTKi is used. Late-onset dysgeusia (taste changes) also presents management challenges, as does fatigue, which can be difficult to distinguish from CLL-related symptoms or other comorbidities in elderly patients. These more persistent adverse events sometimes require dose modifications or discontinuation when they significantly impact quality of life, representing the most frustrating management scenarios for clinicians.
Related Content:
