Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report

Cardio-Oncology

Research

Junu Bae¹  Ashlee Asada²  Ankur Sheel²  Ragavendra R. Baliga³  Kristin L. Koenig⁴  Gregory A. Otterson⁵ 

[1] College of Medicine, The Ohio State University, 43210, Columbus, OH, USA;Department of Internal Medicine, The Ohio State University Wexner Medical Center, 43210, Columbus, OH, USA;Division of Cardiovascular Medicine, Department of Internal Medicine, Cardio-Oncology Center of Excellence, The Ohio State University Wexner Medical Center, OH, 43210, Columbus, OH, USA;Division of Hematology, Department of Medicine, The Ohio State University and The Ohio State University Comprehensive Cancer Center, 43210, Columbus, OH, USA;Division of Oncology, Department of Internal Medicine, The Ohio State University and The Ohio State University Comprehensive Cancer Center, 43210, Columbus, OH, USA;

关键词: Decitabine/Cedazuridine;    Chronic Myelomonocytic leukemia;    Cardio-oncology;    Cardiomyopathy;   

DOI  :  10.1186/s40959-023-00153-6

 received in 2022-03-18, accepted in 2023-01-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHypomethylating agents (HMAs) have shown efficacy in the treatment of hematological malignancies and are indicated for the treatment of chronic myelomonocytic leukemia (CMML). While the HMA decitabine, in its intravenous formulation, has been used since 2006 for the treatment of CMML, use of its oral formulation has been limited by poor bioavailability due to first-pass metabolism by the enzyme cytidine deaminase. The dose of intravenous decitabine is limited by toxicities such as cardiomyopathy and heart failure. Therefore, cedazuridine was developed as an inhibitor of cytidine deaminase. Cedazuridine decreases the first-pass metabolism of oral decitabine allowing therapeutic levels to be achieved at lower doses, and thus, the novel oral combination of cedazuridine with decitabine was developed. While cardiomyopathy and heart failure are well-established adverse effects associated with intravenous decitabine alone, there to our knowledge there have been no documented incidences of reversible cardiomyopathy in the literature or in patients who participated in the phase 2 and phase 3 clinical trials of oral decitabine-cedazuridine.CaseThis case study presents an 85 year-old Caucasian female with CMML who developed cardiomyopathy and heart failure with reduced ejection fraction after completing 5 cycles of therapy with decitabine/cedazuridine. Furthermore, her symptoms and cardiac function recovered upon discontinuation of the drug.ConclusionsWe present an occurrence of reversible cardiomyopathy in a patient who completed 5 cycles of decitabine/cedazuridine, an oral combination therapy developed to enhance oral bioavailability of decitabine thereby limiting its adverse effects. As the decitabine/cedazuridine combination therapy rises in popularity due to its convenient oral formulation, more trials are needed to understand the prevalence of cardiomyopathy with this drug and to discover preventative strategies for cardiotoxic effects.

【 授权许可】

CC BY   
© The Author(s) 2023

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