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Managing BTK inhibitor treatment-related adverse events in patients with chronic lymphocytic leukaemia - cardiovascular complications and bleeding

Publication at First Faculty of Medicine, Faculty of Medicine in Hradec Králové |


Bruton's tyrosine kinase (BTK) inhibitors have altered the treatment landscape of chronic lymphocytic leukaemia (CLL). These highly eff ective drugs improve not only the prognosis but also the quality of life of CLL patients.

Long-term BTK inhibitor treatment can be limited by specifi c adverse events (AEs) such as cardiovascular (CV) complications or bleeding. Ibrutinib, the fi rst-in-class BTK inhibitor, was discontinued in up to 26% of patients in clinical trials due to AEs.

Therefore, there are continuing eff orts to develop BTK inhibitors with the same eff ectivity but better safety profi le, such as covalent BTKi acalabrutinib and zanubrutinib and non-covalent BTKi pirtobrutinib and nemtabrutinib. The pre-treatment workup for all patients should include CV risk level assessment using scoring systems, e. g., Framingham risk score or SCORE.

In patients with high CV risk levels, next-generation BTK inhibitors or other targeted drugs (venetoclax or idelalisib) are generally preferred over ibrutinib. Patients who experience CV toxicity, particularly atrial fi brillation or heart failure, should be consulted with a cardiologist to defi ne the best treatment algorithm.

In contrast to CV toxicity, the risk of major bleeding events is equal for both ibrutinib and acalabrutinib (2-9% vs. 2-5%) based on data from clinical trials. Regarding prevention of bleeding events, BTK inhibitor treatment should be appropriately held prior to any invasive procedure and cannot be restarted until the risk of bleeding is minimal.

Good knowledge of the patient's current medication and potential interactions is crucial in the prevention of any adverse event. This review describes the mechanisms of pathogenesis of cardiovascular complications and bleeding in BTK inhibitor-treated patients.

It summarises their incidence in selected clinical trials and provides recommendations for managing these AEs in clinical practice.