Cardiotoxicity Secondary to Tyrosine Kinase Inhibitors 2nd Generation in Mexican Patients with Chronic Myeloid Leukemia

In the "Age of inhibitors of tyrosine kinase" the long-term prognosis of patients with chronic myeloid leukemia (CML) it has improved significantly, however a concern clinical are the adverse events in the medium and long term, although the profile cardiac safety has been investigated prospectively, have reported multiple adverse events among which are fluid retention, spillage pleural-pericardial effusion, peripheral pulmonary arterial hypertension, heart failure, QT prolongation, coronary artery disease and . We report our experience in the cardiological monitoring CML patients treated with nilotinib and dasatinib, in the second line of treatment.

Objective: To identify the clinical, electrocardiographic and echocardiographic abnormalities in CML patients treated with nilotinib or dasatinib.

Aims: Identify clinical, electrocardiographic and transthoracic echocardiogram alterations in CML patients treated with nilotinib or dasatinib.

Methods: Clinical evaluation, electrocardiograms and transthoracic echocardiogram were performed to all CML patients on treatment with nilotinib or dasatinib during the period between October 2010 and June 2016, at the beginning of treatment and every 6 and 12 months after that according to the occurrence or not of abnormalities detected at baseline. The exclusion criteria were; clinically significant cardiac disease (congestive heart failure), left ventricular ejection fraction (LVEF) < 45%, past myocardial infarction or unstable angina (during the last 12 months), resting bradycardia (< 50 beats/min), left bundle branch block, ventricular bypass, acquired or congenital long QT syndrome (including family history), QTcF interval > 450 msec, patients taking medications that could extend the QT interval and those who could not discontinue their treatment before initiating nilotinib or dasatinib. The doses used of tyrosine kinase inhibitors were 400 mg every 12 hours for nilotinib and 100 mg every 24 hours for dasatinib per os.

Material and Methods: Of a total of 188 patients (122 nilotinib and dasatinib 66) cardiologically evaluated and monitored, analyzed and presented to patients possessed normal baseline studies 127 patients (86 nilotinib and dasatinib 41 with a median age of 39 and 44 years, respectively), with heart abnormalities developed during treatment with second-generation TKIs.

Results: In our study population we must emphasize the development of a high rate of PAH mostly mild during treatment, predominantly in the group with dasatinib, occurring in 12 patients (29%), while nilotinib PAH occurred in 18 patients ( 24%). treatment in patients with moderate or severe recurrent to dose adjustment of dasatinib or nilotinib HAP was discontinued, no QT syndrome acquired long observed in any of the patients. Another finding that mention was the appearance of mild pericarditis and pericardial effusion in a 7 and 2% respectively, dasatinib and nilotinib similar.

Summary/Conclusion: The cardiac adverse events in patients with CML undergoing treatment with second-generation TKI are not common and may be related to factors independent from treatment like age, cardiopulmonary and metabolic comorbidities and pharmacological interactions. So in our experience, the results differ significantly from internationally published and should alert us to the need for a systematic basal cardiac monitoring and tracking routine, which can be timely detect and manage these complications due course as it has been performed in our hospital. To our knowledge is the first report to adverse events in México for PAH secondary to second-generation TKIs.