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

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.
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Contributor : Régis Guieu <>
Submitted on : Tuesday, February 16, 2021 - 4:30:25 PM
Last modification on : Monday, February 22, 2021 - 7:18:13 PM

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Charles Dolladille, Stephane Ederhy, Stéphane Allouche, Quentin Dupas, Radj Gervais, et al.. Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors. Journal for Immunotherapy of Cancer, BMJ Publishing Group 2020, 8 (1), pp.e000261. ⟨10.1136/jitc-2019-000261⟩. ⟨hal-03143214⟩

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