Journal article
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
PloS one, Vol.16(9), pp.e0257189-e0257189
09/15/2021
DOI: 10.1371/journal.pone.0257189
PMCID: PMC8443042
PMID: 34525116
Abstract
BackgroundCardiac 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 findingsWe 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.ConclusionDelaying 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.
Details
- Title: Subtitle
- Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement
- Creators
- Mélanie Bézard - Assistance Publique – Hôpitaux de ParisSilvia Oghina - Assistance Publique – Hôpitaux de ParisDamien Vitiello - Centre National de la Recherche ScientifiqueMounira Kharoubi - Assistance Publique – Hôpitaux de ParisEkaterini Kordeli - Centre National de la Recherche ScientifiqueArnault Galat - Assistance Publique – Hôpitaux de ParisAmira Zaroui - Assistance Publique – Hôpitaux de ParisSoulef Guendouz - Assistance Publique – Hôpitaux de ParisFloriane Gilles - Assistance Publique – Hôpitaux de ParisJason Shourick - Université Paris-Est CréteilDavid Hamon - Assistance Publique – Hôpitaux de ParisVincent Audard - Assistance Publique – Hôpitaux de ParisEmmanuel Teiger - Assistance Publique – Hôpitaux de ParisElsa Poullot - Institut Mondor de Recherche BiomédicaleValérie Molinier-Frenkel - Institut Mondor de Recherche BiomédicaleFrançois Lemonnier - Centre Hospitalier Universitaire Henri-MondorOnnik Agbulut - Centre National de la Recherche ScientifiqueFabien Le Bras - Centre Hospitalier Universitaire Henri-MondorThibaud Damy - Assistance Publique – Hôpitaux de Paris
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.16(9), pp.e0257189-e0257189
- Publisher
- Public Library of Science
- DOI
- 10.1371/journal.pone.0257189
- PMID
- 34525116
- PMCID
- PMC8443042
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Language
- English
- Date published
- 09/15/2021
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984691517302771
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