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

Charles Dolladille, Stephane Ederhy, Stéphane Allouche, Querntin Dupas, Radj Gervais, Jeannick Madelaine, Marion Sassier, Anne-Flore Plane, Francois Comoz, Ariel Aron Cohen, Franck Roland Thuny, Jennifer Cautela, Joachim Alexandre, Charles Dolladille, Stephane Ederhy, Stéphane Allouche, Querntin Dupas, Radj Gervais, Jeannick Madelaine, Marion Sassier, Anne-Flore Plane, Francois Comoz, Ariel Aron Cohen, Franck Roland Thuny, Jennifer Cautela, Joachim Alexandre

Abstract

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.

Keywords: cardiology; epidemiology; pharmacology.

Conflict of interest statement

Competing interests: None declared.

© 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.

Figures

Figure 1
Figure 1
Flowchart of case selection for the French cardio-oncology units and VigiBase. CAE, cardiac adverse event; ICI, immune checkpoint inhibitor; ICSR, individual case safety report.
Figure 2
Figure 2
Immune checkpoint inhibitor-associated CAE rates in early (

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Source: PubMed

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