Acute cardiotoxicity in pediatric and adolescent patients with solid tumors treated with tyrosine kinase inhibitors

Background: Multitargeted tyrosine kinase inhibitors (MTKIs) have increasingly been used for the treatment of pediatric and young adult patients with solid tumors. Whereas cardiac toxicity is documented in adults, data remain limited in pediatrics. This study sought to characterize the incidence and outcomes of acute cardiotoxicity in pediatric patients with solid tumors treated with an MTKI. Methods: A retrospective review was conducted of patients who received MTKIs from 2000 to 2021 at St. Jude Children's Research Hospital. Analyses included patient and disease characteristics, treatment specifics, and measurements of cardiotoxicity (ejection fraction [EF], <55%; global longitudinal strain [GLS], -17 to 0; z scores, >2 for left atrial end-systolic volume index, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter). Hypertension (HTN) was evaluated independently, and defined with American Academy of Pediatrics clinical practice guidelines and American College of Cardiology/American Heart Association HTN guidelines. Results: Among 112 patients, 73 (65%) underwent echocardiography during MTKI therapy. Of 56 patients without prior cardiotoxicity, 17 (32.1%) developed cardiac toxicity during treatment. Of 48 patients without preexisting HTN, 36 (72%) developed HTN at 6 months. Abnormal GLS was the most frequent new-onset cardiac finding (29.5% at 6 months). Of 61 patients with sequential echocardiograms, 51.4% had a >= 5% decline in EF but only 3.6% required MTKI dose reductions as a result of cardiotoxicity. Conclusions: Despite changes in cardiac function while on MTKIs, reductions because of cardiac toxicity were infrequent. Routine monitoring of cardiac function during MTKI use and early intervention may enable patients to continue therapy while safeguarding cardiovascular health.