My Treatment Approach: Shared Decision-Making in CLL: Balancing Safety, Efficacy, and Patient Preference in CLL - Episode 4
Identifying BTKi Treatment-Related Adverse Events
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 but can sometimes develop later, with dose-reduction strategies being effective for maintaining efficacy while managing tolerability across first- and second-generation BTKis.
This segment focuses on identifying and managing Bruton tyrosine kinase inhibitor (BTKi) treatment-related adverse events in patients with chronic lymphocytic leukemia (CLL). The discussion emphasizes that most BTKi adverse effects typically occur early in treatment, with rash being a common example that usually appears soon after initiation. However, the timing can vary, and late-onset adverse events are possible, requiring careful evaluation to distinguish drug-related effects from other causes such as concurrent medications or unrelated conditions. When managing adverse events like rash, dose-reduction strategies are often effective, particularly with ibrutinib, where reducing from 420 mg to 280 mg maintains efficacy while potentially alleviating symptoms.
The experts identify several BTKi class effects that occur across all agents in this drug class, though with varying frequencies between first- and second-generation inhibitors. Universal class effects include cardiovascular complications (less common with newer agents), hypertension, bleeding tendency due to platelet dysfunction, diarrhea, and skin fragility leading to easy bruising and hematomas. While second-generation BTKis generally demonstrate improved safety profiles with lower incidence rates of these adverse events, they are not completely eliminated. Headache appears to be more specifically associated with acalabrutinib, though it can occasionally occur with other BTKis as well.
Hypertension represents a unique challenge among BTKi adverse events because it can develop at any time during treatment, including after years of stable therapy. Unlike most other adverse effects that occur early and may resolve, hypertension incidence continues to increase over time with ibrutinib, requiring ongoing monitoring even in patients who have been stable on treatment for extended periods. The long-term hypertension risk profile for newer BTKis remains less clear due to shorter follow-up periods compared with ibrutinib’s decade of clinical experience, though similar patterns may emerge with extended use of second-generation agents.
Related Content:
