PREVENCE A LÉČBA KARDIOVASKULÁRNÍCH A KRVÁCIVÝCH KOMPLIKACÍ U NEMOCNÝCH S CHRONICKOU LYMFOCYTÁRNÍ LEUKEMIÍ LÉČENÝCH INHIBITORY BRUTONOVY KINÁZY
Keywords:
acalabrutinib – arterial hypertension – BTK inhibitor – atrial fibrillation – chronic lymphocytic leukemia – ibrutinib – bleedingAbstract
Brutonˈs tyrosine kinase (BTK) inhibitors have altered the treatment landscape of chronic lymphocytic leukaemia (CLL). These highly effective drugs improve not only prognosis but also the quality of life of CLL patients. Long-term BTK inhibitor treatment can be limited by specific adverse events (AEs) such as cardiovascular (CV) complications or bleeding. Ibrutinib, the first-in-class BTK inhibitor, was discontinued in up to 26 % of patients in clinical trials due to AEs. Therefore we witness continuing efforts to develop BTK inhibitors with the same effectivity but better safety profile, such as covalent BTKi acalabrutinib and zanubrutinib and non-covalent BTKi pirtobrutinib and nemtabrutinib. The pretreatment 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 level, next-generation BTK inhibitors or other targeted drugs (venetoclax or idelalisib) are generally preferred over ibrutinib. Patients who experience CV toxicity, particularly atrial fibrillation or heart failure, should be consulted with a cardiologist to define 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 any invasive procedure and cannot be restarted until the risk of bleeding is minimal. Good knowledge of patientˈs current medication and potential interactions is crucial in prevention of any adverse event. This review describes the mechanisms of pathogenesis of cardiovascular complications and bleeding in BTK inhibitor-treated patients, summarises their incidence in selected clinical trials and provides recommendations for managing these AEs in clinical practice.
