Midostaurin-associated perimyocarditis: a case report of severe cardiotoxicity of novel targeted treatments for acute myeloid leukaemia and review of the literature.

Abstract

Background: Midostaurin is a multikinase inhibitor for the treatment of Fms-like tyrosine 3 (FLT3)-mutated acute myeloid leukaemia (AML). Cardiac adverse events like QTc-prolongation, pericardial effusion, and congestive heart failure have been described. Inflammatory diseases associated with midostaurin are rarely reported.

Case summary: A 24-year-old man with newly diagnosed AML and FLT3-ITD mutation was treated with intensive remission-induction chemotherapy and midostaurin. After 5 days of midostaurin, the patient reported severe focal chest pain. Due to laboratory evidence of acute myocardial cell damage, coronary macroangiopathy and pulmonary artery embolism were ruled out via computed tomography. Cardiovascular magnetic resonance showed evidence for active perimyocarditis with myocardial oedema and late gadolinium of the basal, midventricular, and apical lateral wall of the left ventricle. Therapeutic drug monitoring did not reveal excessive midostaurin plasma levels, and hence, initially suspected drug interaction with posaconazole administered for antifungal prophylaxis was considered less likely to be causative. After discontinuing midostaurin, clinical signs of perimyocarditis improved. During continued high-dose cytarabine therapy, no further cardiac events occurred. It was concluded that perimyocarditis was an adverse effect of midostaurin since the inhibition of FTL3 may have led to a loss of cardiomyocyte protective capacity against oxidative stress-induced apoptosis, as previously described in vitro.

Discussion: In addition to the most frequently reported non-cardiac adverse effects of midostaurin, serious cardiotoxic complications appear to occur and may require discontinuation of therapy. This case highlights the importance of interdisciplinary work-up of a cardio-oncology pathway even in presumably low-risk patients and particularly in the context of rare cases of cardiotoxicity in novel cancer treatments.