Onkologie. 2023:17(5):357-362 | DOI: 10.36290/xon.2023.067

Cardiovascular side effects of signaling pathway inhibitors in chronic lymphocytic leukemia therapy

Peter Turcsányi¹, Eva Kriegová², Tomáš Papajík¹

¹ Hemato‑onkologická klinika, LF UP a FN Olomouc

² Ústav imunologie, LF UP a FN Olomouc

Treatment of chronic lymphocytic leukemia (CLL) is becoming more targeted and effective due to signaling pathway inhibitors. Although many patients achieve excellent treatment responses, targeting the malignant cell is not absolute and a variety of side effects are encountered. With the introduction of the first-generation Bruton's tyrosine kinase inhibitors (BTKi), there has been increasing concern about the risk of cardiovascular (CV) side effects, including atrial fibrillation (AF), hypertension (HTN) and heart failure. With second and third generation BTKi, CV risks are lower, but data are limited by shorter observation. It has been shown that treatment with some BTKi may worsen the course of CV disease in at-risk patients, and therefore it is essential to evaluate the individual risks in each patient, including CV disease history, risk factors and electrocardiogram (ECG) before starting targeted therapy. In patients at high CV risk and being considered for BTKi therapy, multidisciplinary consultation is appropriate, with preference for more selective BTKi, including acalabrutinib and zanubrutinib. Patients with a history of heart failure should generally avoid BTKi therapy. Patients with a history of ventricular arrhythmias should not be treated with ibrutinib; the risk of complications with next-generation BTKi therapy is not reliably known. Patients treated with BTKi should be regularly monitored for the development of potential CV complications such as heart failure, arrhythmias or hypertension. For a comprehensive view, all groups of the most commonly used signaling pathway inhibitors are included in the review of adverse cardiovascular effects.

Keywords: chronic lymphocytic leukemia, Bruton's tyrosine kinase inhibitors, phosphatidylinositol-3 kinase inhibitors (PI3Ki), B-cell receptor 2 inhibitors (BCL-2i), cardiovascular disease, hypertension, cardiac arrhythmias, heart failure.

Accepted: November 28, 2023; Published: November 29, 2023  Show citation