Lifelong TKI therapy: how to manage cardiovascular and other risks

Abstract

Beginning with imatinib and now spanning 6 oral, highly active, and mostly safe agents, the development of specific targeted therapy for patients with chronic myeloid leukemia (CML) has created a new world featuring chronic maintenance chemotherapy for all treated as such, treatment-free remission, and functional cure after prolonged deep remission in a subset. As a result comes a necessary shift in focus from acute to chronic toxicity, increasing attention to patient comorbidities, and critical thinking around specific adverse events such as metabolic, cardiovascular, and cardiopulmonary effects, which vary from agent to agent. This review aims to pull together the state of the art of managing the “C” in CML—a chronic myeloproliferative neoplasm treated at present over many years with oral BCR-ABL-targeted agents in a population whose overall health can be complex and potentially affected by disease and therapy—and determine how we can better manage a highly treatable and increasingly curable cancer.

The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia

“…Finally, a potential strategy to reduce VAE risk among patients with CML could be the discontinuation of TKI treatment [ 35 ]. The global time of TKI treatment is an important variable when considering if a patient is eligible for TKI discontinuation, as is the duration of a deep molecular response, both associated with a higher probability of treatment-free remission [ 36 ].…”

Haematological Drugs Affecting Lipid Metabolism and Vascular Health

“…The treatment of chronic myeloid leukaemia (CML) has been revolutionised with the introduction of oral tyrosine kinase inhibitors (TKIs). It should be remembered that following approval of TKIs for the treatment of CML, the overall survival of these patients improved to 70% [ 14 ]. Imatinib (a first-generation inhibitor) can reduce serum levels of proatherogenic LDL and can normalise plasma lipid levels in hypercholesterolemic and hypertriglyceridemic patients [ 15 ].…”

In vivo imaging system (IVIS) therapeutic assessment of tyrosine kinase inhibitor-loaded gold nanocarriers for acute myeloid leukemia: a pilot study

“…RATIFY (NCT00651261), a phase III trial, showed that MDS addition to chemotherapy improves survival in FLT3-mutated patients (Stone et al, 2017). Although TKI first-line therapy is used for myelosuppression to induce a hematological response, several side effects like liver dysfunction, edema, fluid retention, fatigue, and gastrointestinal symptoms (Guilhot et al, 2012;Qosa et al, 2018;Mauro, 2021) might occur. On the other hand, chemotherapy usually induces serious side effects that augment in combination with other drugs by becoming acute.…”