My Treatment Approach: Shared Decision-Making in CLL: Balancing Safety, Efficacy, and Patient Preference in CLL - Episode 7
Coordinating CLL Care to Identify BTKi Intolerance and Manage Toxicities
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 through dose-modification strategies that have become preferred over drug switching, emphasizing that intolerance is subjectively defined by patient acceptance and requires a multidisciplinary team approach including extensive patient education, close monitoring by nurses and pharmacists, and collaboration with cardio-oncology specialists to manage cardiovascular toxicities, with the notable exception that ventricular arrhythmias like PVCs warrant immediate consideration for drug discontinuation due to risk of sudden death.
This segment addresses the complex challenge of defining Bruton tyrosine kinase inhibitor (BTKi) intolerance and coordinating care to manage associated toxicities in patients with chronic lymphocytic leukemia (CLL). The experts acknowledge that intolerance is a subjective concept, with the most practical definition being when patients refuse to continue taking the medication. Intolerance typically results from recurrent minor adverse events that patients find unacceptable rather than single severe events. For serious cardiovascular adverse effects like atrial fibrillation or hypertension, switching within the BTKi class may not provide significant benefit since these are considered class effects, and patients who develop these complications have already demonstrated high-risk profiles.
The discussion highlights specific scenarios where switching between BTKis is warranted, particularly for patients experiencing palpitations with premature ventricular contractions (PVCs) on electrocardiogram. This represents one of the few clear indications for switching from ibrutinib to a second-generation BTKi due to concerns about rare but serious ventricular arrhythmias and sudden death. If cardiac symptoms persist despite the switch, complete discontinuation of BTKi therapy may be necessary. The experts emphasize the importance of recognizing these potentially life-threatening cardiac complications, especially given that patients with CLL are expected to have decades of remaining life expectancy.
The management of BTKi therapy requires a comprehensive multidisciplinary approach centered on patient education. Health care teams, including pharmacists, nurse practitioners, physician assistants, and administrative staff, play crucial roles in educating patients about expected adverse effects and maintaining close communication to prevent unnecessary emergency department visits. The strategy involves thorough pretreatment counseling about potential adverse events, establishing clear communication channels for early intervention, and coordinating with cardio-oncology specialists when cardiovascular complications arise. This educational approach helps patients understand that many adverse effects are temporary and manageable, while also ensuring prompt recognition and management of serious complications that require immediate attention or treatment modifications.
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