A New Paradigm of Cardio-Hematological Monitoring in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors

Abstract

Significant progress has been achieved in treating patients with onco-hematological diseases, including chronic myeloid leukemia (CML). This is primarily associated with the development of targeted therapy involving tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, bosutinib, dasatinib, and ponatinib. Along with the increased survival of patients with CML, special attention has recently been paid to cardiovascular complications in CML patients due to the prevalence of cardiovascular diseases in the general population and the toxicity profile of targeted drugs. This article presents the strategy for reducing cardiovascular risk in CML patients treated with TKIs. We discuss the components of cardiovascular risk in CML patients and the findings of current studies. Current data confirm the increased cardiovascular risk in the CML population compared to the general population, which necessitates the widespread introduction of cardiovascular prevention strategies in CML patients. The pharmacokinetics and pharmacodynamics of TKIs on the cardiovascular system are discussed. We propose two main approaches in the strategy of cardiovascular risk prevention in patients with CML, namely, before the start of TKI administration and during TKI treatment. This article presents the diagnostic assessment before prescribing TKIs, as well as while monitoring TKI therapy, and discusses the features of the choice of TKIs depending on patients' general and cardiovascular comorbidity. Emphasis is placed on the risk stratification in patients with CML following general population algorithms, lifestyle modifications, and statin therapy for achieving the target levels of cardiovascular indicators. We also discuss unsolved questions in the current clinical guidelines and ways to further develop a cardiovascular risk-reducing strategy for CML patients.

Addendum to the German Consensus Recommendations on Ponatinib in the Treatment of Chronic Myeloid Leukemia

“…However, compared to imatinib, the more potent second- and third-generation TKIs are associated with a potential increase in cardiovascular (CV) risk to different extents, particularly arterial occlusive events (AOEs) [ 4 ]. However, each TKI may have a different cardiac and/or vascular toxicity profile in patients depending on their age, sex, comorbidities, and the presence of additional common CV risk factors (e.g., smoking, dyslipidemia, overweight, unhealthy lifestyle, diabetes mellitus) [ 5 ]. Differences in the inhibitory off-target effects of tyrosine kinases other than BCR::ABL1 may also determine their distinct toxicity profiles [ 5 ].…”

“…However, each TKI may have a different cardiac and/or vascular toxicity profile in patients depending on their age, sex, comorbidities, and the presence of additional common CV risk factors (e.g., smoking, dyslipidemia, overweight, unhealthy lifestyle, diabetes mellitus) [ 5 ]. Differences in the inhibitory off-target effects of tyrosine kinases other than BCR::ABL1 may also determine their distinct toxicity profiles [ 5 ]. The newly approved STAMP (specifically targeting the ABL myristoyl pocket) inhibitor asciminib – which is indicated for the treatment of CP-CML after failure of two or more TKIs – appears to have a favorable CV safety profile [ 6 ].…”