Cargando…
Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report
BACKGROUND: Hypomethylating 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, us...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845814/ https://www.ncbi.nlm.nih.gov/pubmed/36653885 http://dx.doi.org/10.1186/s40959-023-00153-6 |
_version_ | 1784870998773858304 |
---|---|
author | Sheel, Ankur Bae, Junu Asada, Ashlee Otterson, Gregory A. Baliga, Ragavendra R. Koenig, Kristin L. |
author_facet | Sheel, Ankur Bae, Junu Asada, Ashlee Otterson, Gregory A. Baliga, Ragavendra R. Koenig, Kristin L. |
author_sort | Sheel, Ankur |
collection | PubMed |
description | BACKGROUND: Hypomethylating 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. CASE: This 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. CONCLUSIONS: We 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. |
format | Online Article Text |
id | pubmed-9845814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98458142023-01-18 Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report Sheel, Ankur Bae, Junu Asada, Ashlee Otterson, Gregory A. Baliga, Ragavendra R. Koenig, Kristin L. Cardiooncology Research BACKGROUND: Hypomethylating 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. CASE: This 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. CONCLUSIONS: We 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. BioMed Central 2023-01-18 /pmc/articles/PMC9845814/ /pubmed/36653885 http://dx.doi.org/10.1186/s40959-023-00153-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sheel, Ankur Bae, Junu Asada, Ashlee Otterson, Gregory A. Baliga, Ragavendra R. Koenig, Kristin L. Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
title | Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
title_full | Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
title_fullStr | Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
title_full_unstemmed | Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
title_short | Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
title_sort | reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845814/ https://www.ncbi.nlm.nih.gov/pubmed/36653885 http://dx.doi.org/10.1186/s40959-023-00153-6 |
work_keys_str_mv | AT sheelankur reversiblecardiomyopathyinapatientwithchronicmyelomonocyticleukemiatreatedwithdecitabinecedazuridineacasereport AT baejunu reversiblecardiomyopathyinapatientwithchronicmyelomonocyticleukemiatreatedwithdecitabinecedazuridineacasereport AT asadaashlee reversiblecardiomyopathyinapatientwithchronicmyelomonocyticleukemiatreatedwithdecitabinecedazuridineacasereport AT ottersongregorya reversiblecardiomyopathyinapatientwithchronicmyelomonocyticleukemiatreatedwithdecitabinecedazuridineacasereport AT baligaragavendrar reversiblecardiomyopathyinapatientwithchronicmyelomonocyticleukemiatreatedwithdecitabinecedazuridineacasereport AT koenigkristinl reversiblecardiomyopathyinapatientwithchronicmyelomonocyticleukemiatreatedwithdecitabinecedazuridineacasereport |