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

Abstract

BackgroundImmune 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.MethodsFirst, 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.ResultsIn 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).ConclusionsLate CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD.Trial registration numbersNCT03678337,NCT03882580, andNCT03492528.

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

“…Disproportionality analysis stated but not shown Moslehi et al (2018); Vigibase [ 35 ] Myocarditis 46% (higher in combo vs. monotherapies) Median TTO = 27 (data for 33 patients) 101 cases (57% with anti-PD-1). Concurrent irAEs in 42% (myositis, myasthenia gravis) Dolladille et al (2020); Vigibase [ 52 ] Cardiac events 30–27% (early and late events) Median TTO = 21 (early cases)—178 (late cases) for Vigibase; median TTO = 14 (early cases)—104 (late cases) in three French cardio-oncology units 437 early cases (onset < 90 days), 159 late cases (onset ≥ 90 cases); almost exclusively with anti-PD-1/PD-L1. Late cases had significantly more frequent HF (21.1% vs. 31.4%).…”

Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues

“…Seeing the high mortality rates of nearly 50%, the baseline value and continuous cTn monitoring throughout the cancer treatment become even more crucial [50]. Furthermore, concerns have been raised about late IRCAE occurring 90 days after the start of ICI treatment [51]. Patients diagnosed with late IRCAE mostly show symptoms and signs of heart failure and not myocarditis.…”

Myocarditis Induced by Immune Checkpoint Inhibitors: Mechanisms and Therapeutic Prospects

“… 97 Compared with ICI-mediated early immunomyocarditis (occurring in the first 90 days of treatment), ICI-mediated late immunomyocarditis (after the first 90 days of treatment) is more likely to develop heart failure. 98 Although the incidence of immunomyocarditis is not high, the mortality rate of immunomyocarditis is the highest of all ICI-mediated side effects. Wang et al retrospectively analyzed 613 cases of fatal ICI-mediated side effects reported from 2009 to 2018 and found that 333 cases were caused by anti-PD-1/PD-L1, and 27 patients (8%) died from immunomyocarditis.…”