Cargando…

Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement

BACKGROUND: Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP l...

Descripción completa

Detalles Bibliográficos
Autores principales: Bézard, Mélanie, Oghina, Silvia, Vitiello, Damien, Kharoubi, Mounira, Kordeli, Ekaterini, Galat, Arnault, Zaroui, Amira, Guendouz, Soulef, Gilles, Floriane, Shourick, Jason, Hamon, David, Audard, Vincent, Teiger, Emmanuel, Poullot, Elsa, Molinier-Frenkel, Valérie, Lemonnier, François, Agbulut, Onnik, Le Bras, Fabien, Damy, Thibaud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443042/
https://www.ncbi.nlm.nih.gov/pubmed/34525116
http://dx.doi.org/10.1371/journal.pone.0257189
_version_ 1783753111310958592
author Bézard, Mélanie
Oghina, Silvia
Vitiello, Damien
Kharoubi, Mounira
Kordeli, Ekaterini
Galat, Arnault
Zaroui, Amira
Guendouz, Soulef
Gilles, Floriane
Shourick, Jason
Hamon, David
Audard, Vincent
Teiger, Emmanuel
Poullot, Elsa
Molinier-Frenkel, Valérie
Lemonnier, François
Agbulut, Onnik
Le Bras, Fabien
Damy, Thibaud
author_facet Bézard, Mélanie
Oghina, Silvia
Vitiello, Damien
Kharoubi, Mounira
Kordeli, Ekaterini
Galat, Arnault
Zaroui, Amira
Guendouz, Soulef
Gilles, Floriane
Shourick, Jason
Hamon, David
Audard, Vincent
Teiger, Emmanuel
Poullot, Elsa
Molinier-Frenkel, Valérie
Lemonnier, François
Agbulut, Onnik
Le Bras, Fabien
Damy, Thibaud
author_sort Bézard, Mélanie
collection PubMed
description BACKGROUND: Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment. METHODS AND FINDINGS: We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement. CONCLUSION: Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation.
format Online
Article
Text
id pubmed-8443042
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-84430422021-09-16 Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement Bézard, Mélanie Oghina, Silvia Vitiello, Damien Kharoubi, Mounira Kordeli, Ekaterini Galat, Arnault Zaroui, Amira Guendouz, Soulef Gilles, Floriane Shourick, Jason Hamon, David Audard, Vincent Teiger, Emmanuel Poullot, Elsa Molinier-Frenkel, Valérie Lemonnier, François Agbulut, Onnik Le Bras, Fabien Damy, Thibaud PLoS One Research Article BACKGROUND: Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment. METHODS AND FINDINGS: We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement. CONCLUSION: Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation. Public Library of Science 2021-09-15 /pmc/articles/PMC8443042/ /pubmed/34525116 http://dx.doi.org/10.1371/journal.pone.0257189 Text en © 2021 Bézard et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bézard, Mélanie
Oghina, Silvia
Vitiello, Damien
Kharoubi, Mounira
Kordeli, Ekaterini
Galat, Arnault
Zaroui, Amira
Guendouz, Soulef
Gilles, Floriane
Shourick, Jason
Hamon, David
Audard, Vincent
Teiger, Emmanuel
Poullot, Elsa
Molinier-Frenkel, Valérie
Lemonnier, François
Agbulut, Onnik
Le Bras, Fabien
Damy, Thibaud
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
title Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
title_full Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
title_fullStr Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
title_full_unstemmed Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
title_short Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
title_sort dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443042/
https://www.ncbi.nlm.nih.gov/pubmed/34525116
http://dx.doi.org/10.1371/journal.pone.0257189
work_keys_str_mv AT bezardmelanie dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT oghinasilvia dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT vitiellodamien dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT kharoubimounira dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT kordeliekaterini dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT galatarnault dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT zarouiamira dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT guendouzsoulef dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT gillesfloriane dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT shourickjason dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT hamondavid dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT audardvincent dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT teigeremmanuel dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT poullotelsa dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT molinierfrenkelvalerie dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT lemonnierfrancois dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT agbulutonnik dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT lebrasfabien dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement
AT damythibaud dexamethasoneisassociatedwithearlydeathsinlightchainamyloidosispatientswithseverecardiacinvolvement