Cardiovascular, pulmonary, and metabolic toxicities complicating tyrosine kinase inhibitor therapy in chronic myeloid leukemia: Strategies for monitoring, detecting, and managing

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. Beyond matching patient disease profiles with TKI specificity, differences in the efficacy and toxicity profiles and a patient's comorbid risk factors should be considered when selecting the most appropriate agent. Our objectives are to review the incidence and severity of cardiovascular, metabolic, and pulmonary disorders associated with these TKIs, highlighting differences in adverse event profiles, suggested risk-mitigation strategies, and guidance for TKI selection in different settings. Patients receiving TKI agents for CML should be monitored for signs and symptoms of toxicity throughout therapy. Preemptive assessment, early toxicity recognition, and prompt management of cardiovascular, metabolic, and pulmonary toxicities can minimize treatment-limiting complications and improve outcomes in patients with CML.

Pretreatment evaluation of fluorescence resonance energy transfer‐based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib

“…The off-target effect may be associated with potential adverse events such as cardiovascular, metabolic and pulmonary toxicities, and the spectrum of adverse events varies among these TKI. 15 In the current situation, the choice of a TKI for first-line treatment is generally based on the patient's comorbidities and disease status. 16 The Sokal or Hasford risk score is generally used to estimate disease status, and a high risk is associated with a low rate of cytogenetic and molecular remission and with a high rate of disease progression.…”

Ponatinib and platelets a conflict in CML

“…Heart failure, including fatal cases, occurred in 9% of ponatinib-treated patients. 2 To explore the vascular toxicity due to endothelial alterations from ponatinib, Lafiti et al used in vivo ultrasound molecular imaging and intravital microscopy. The animal models included a wild-type C57Bl/6 mouse and a hyperlipidemic mouse harboring the apoliprotein-E gene deletion (ie, ApoE 2/2 mice).…”

Tyrosine Kinase Inhibitor–Induced Pulmonary Arterial Hypertension

“…Chronic myeloid leukemia (CML) is a myeloproliferative disease resulting from the activation of the BCR-ABL1 oncogene. 1 The incidence of CML increases with age and is estimated at 1.75 per 100,000 in the United States. 2 CML is characterized by the presence of the chromosomal translocation t (9;22), leading to the formation of the Philadelphia (Ph) chromosome.…”

“…19 Investigating TKI toxicity is very important, as patients with CML may require lifelong treatment with a TKI and because some complications can be fatal if not diagnosed and treated expediently. 1 The most frequently described side effects of TKI therapy involve the cardiovascular, metabolic, and pulmonary systems such as QT interval prolongation, heart failure, sudden death, systemic arterial hypertension, thrombotic events, peripheral arterial occlusive disease, hepatic failure, dyslipidemia, hyperglycemia, pneumonitis, pulmonary arterial hypertension (PAH), and pleural effusions ( Table 1). 1,10 These complications can appear within the first months or even years after the treatment initiation.…”

“…1 The most frequently described side effects of TKI therapy involve the cardiovascular, metabolic, and pulmonary systems such as QT interval prolongation, heart failure, sudden death, systemic arterial hypertension, thrombotic events, peripheral arterial occlusive disease, hepatic failure, dyslipidemia, hyperglycemia, pneumonitis, pulmonary arterial hypertension (PAH), and pleural effusions ( Table 1). 1,10 These complications can appear within the first months or even years after the treatment initiation. 20 Interestingly, imatinib showed encouraging results in animal studies as a treatment for PAH, having properties such as blocking platelet-derived growth factor and c-KIT signaling, which are involved in PAH pathogenesis.…”