Comprehensive Approaches for Managing Therapeutic Safety in TN CLL

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BTK inhibitor toxicity management requires careful patient risk stratification and proactive monitoring strategies, particularly for cardiovascular complications. Class effects of covalent BTK inhibitors include hypertension, bleeding, and cardiac arrhythmias, with atrial fibrillation and potential sudden cardiac death representing the most serious concerns. Patients with cardiac risk factors benefit from cardio-oncology consultation for risk assessment and cardiac optimization before treatment initiation. Regular monitoring includes baseline and follow-up electrocardiograms (ECGs), ECGs when indicated, and home blood pressure monitoring to avoid white coat hypertension in clinic settings.

Collaboration with cardiology colleagues proves invaluable for optimizing patient care, often revealing opportunities to streamline antiplatelet therapy and switch patients from warfarin to direct oral anticoagulants when appropriate. The combination of warfarin with BTK inhibitors represents a relative contraindication due to increased bleeding risk. Chronic toxicities affecting quality of life, including diarrhea, fatigue, joint pain, and muscle spasms, warrant attention and management strategies rather than dismissal as mere nuisances.

Dose reduction strategies and drug holidays can effectively manage chronic BTK inhibitor toxicities while maintaining disease control. A 1- to 2-week treatment break often helps distinguish drug-related symptoms from other causes, and many patients can achieve long-term control at reduced doses. For fixed-duration combinations, toxicity management becomes more complex as BTK inhibitor adverse effects can occur early in treatment, but the defined end point makes toxicity tolerance discussions easier with patients. Growth factor support helps maintain venetoclax dose intensity during neutropenic episodes, balancing infection risk against treatment efficacy goals.