Acute cardiotoxicity after initiation of the novel tyrosine kinase inhibitor gilteritinib for acute myeloid leukemia

Abstract

Background: Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib may be associated with underrecognized cardiotoxicities.

Case presentation: This case describes a patient with a history significant for hyperlipidemia who was diagnosed with relapsed acute myeloid leukemia. After four doses of gilteritinib monotherapy, she abruptly developed acute systolic heart failure with global hypokinesis and septal wall motion abnormalities. Two days after discontinuation, cardiac magnetic resonance imaging showed partial recovery of her left ventricular ejection fraction as well as myocardial edema and non-ischemic fibrosis suggestive of inflammatory cardiomyopathy. She underwent intravenous diuresis and eventually started guideline-directed heart failure therapy. Follow-up cardiac magnetic resonance imaging five months later showed improved ejection fraction with mild non-ischemic fibrosis and resolution of myocardial edema and inflammation. She later received an allogeneic stem cell transplant from a matched unrelated donor.

Conclusions: Gilteritinib may be associated with early cardiotoxicities, including non-ischemic cardiomyopathy and myocarditis. Cardiac magnetic resonance imaging can be an important modality to help differentiate or diagnose early cardiotoxicities associated with novel targeted therapies.

Keywords: Acute myeloid leukemia; Cardiac MRI; Cardio-oncology; FLT3-mutation; Gilteritinib.

Fig. 1

Admission electrocardiogram demonstrating sinus tachycardia (left upper) with negative T waves in leads V1-V3 and admission chest radiograph showing no acute cardiopulmonary disease (left lower). After four doses of gilteritinib and five days after admission, a repeat electrocardiogram is unremarkable (upper right). A repeat chest radiograph demonstrates interval cardiomegaly and diffuse pulmonary interstitial edema (lower right)

Fig. 2

Echocardiogram after four doses of gilteritinib demonstrating acutely reduced systolic function and global hypokinesis. After four doses of gilteritinib targeted therapy, an echocardiogram showed moderately reduced left ventricular systolic function, an estimated ejection fraction of 36% with global hypokinesis and regional abnormalities of the septum

Fig. 3

Cardiac magnetic resonance imaging (MRI) after six days of gilteritinib targeted therapy. After gilteritinib initiation, the patient developed significant clinical heart failure. Cardiac MRI revealed new left ventricular dilation and depressed systolic function with evidence of myocardial edema/ inflammation on T2 mapping (red arrows; max T2 of 70 milliseconds, normal < 53 ms), as well as patchy correlating non-ischemic patterned fibrosis with late gadolinium enhancement (LGE). Myocardial extracellular volume fraction was also elevated (not shown here). However, five months after therapeutic cessation, systolic function normalized with injury resolution (green arrows)