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Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of tr...

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Autores principales: Dolladille, Charles, Ederhy, Stephane, Allouche, Stéphane, Dupas, Querntin, Gervais, Radj, Madelaine, Jeannick, Sassier, Marion, Plane, Anne-Flore, Comoz, Francois, Cohen, Ariel Aron, Thuny, Franck Roland, Cautela, Jennifer, Alexandre, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057417/
https://www.ncbi.nlm.nih.gov/pubmed/31988143
http://dx.doi.org/10.1136/jitc-2019-000261
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author Dolladille, Charles
Ederhy, Stephane
Allouche, Stéphane
Dupas, Querntin
Gervais, Radj
Madelaine, Jeannick
Sassier, Marion
Plane, Anne-Flore
Comoz, Francois
Cohen, Ariel Aron
Thuny, Franck Roland
Cautela, Jennifer
Alexandre, Joachim
author_facet Dolladille, Charles
Ederhy, Stephane
Allouche, Stéphane
Dupas, Querntin
Gervais, Radj
Madelaine, Jeannick
Sassier, Marion
Plane, Anne-Flore
Comoz, Francois
Cohen, Ariel Aron
Thuny, Franck Roland
Cautela, Jennifer
Alexandre, Joachim
author_sort Dolladille, Charles
collection PubMed
description BACKGROUND: Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described. METHODS: First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of <90 days after ICI therapy initiation) and late (defined as a CAE TTO of ≥90 days after ICI therapy initiation) ICI-associated CAE consecutive cases who were referred to three French cardio-oncology units. Second, ICI-associated CAE cases were searched in VigiBase, the WHO global individual case safety report database, and early and late ICI-associated CAEs were compared. RESULTS: In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively). CONCLUSIONS: Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD. TRIAL REGISTRATION NUMBERS: NCT03678337, NCT03882580, and NCT03492528.
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spelling pubmed-70574172020-03-05 Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors Dolladille, Charles Ederhy, Stephane Allouche, Stéphane Dupas, Querntin Gervais, Radj Madelaine, Jeannick Sassier, Marion Plane, Anne-Flore Comoz, Francois Cohen, Ariel Aron Thuny, Franck Roland Cautela, Jennifer Alexandre, Joachim J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described. METHODS: First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of <90 days after ICI therapy initiation) and late (defined as a CAE TTO of ≥90 days after ICI therapy initiation) ICI-associated CAE consecutive cases who were referred to three French cardio-oncology units. Second, ICI-associated CAE cases were searched in VigiBase, the WHO global individual case safety report database, and early and late ICI-associated CAEs were compared. RESULTS: In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively). CONCLUSIONS: Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD. TRIAL REGISTRATION NUMBERS: NCT03678337, NCT03882580, and NCT03492528. BMJ Publishing Group 2020-01-26 /pmc/articles/PMC7057417/ /pubmed/31988143 http://dx.doi.org/10.1136/jitc-2019-000261 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Clinical/Translational Cancer Immunotherapy
Dolladille, Charles
Ederhy, Stephane
Allouche, Stéphane
Dupas, Querntin
Gervais, Radj
Madelaine, Jeannick
Sassier, Marion
Plane, Anne-Flore
Comoz, Francois
Cohen, Ariel Aron
Thuny, Franck Roland
Cautela, Jennifer
Alexandre, Joachim
Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
title Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
title_full Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
title_fullStr Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
title_full_unstemmed Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
title_short Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
title_sort late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057417/
https://www.ncbi.nlm.nih.gov/pubmed/31988143
http://dx.doi.org/10.1136/jitc-2019-000261
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