Underreporting of Major Cardiac Adverse Events With Immune Checkpoint Inhibitors in Clinical Trials: Importance of Postmarketing Pharmacovigilance Surveys

Abstract

Naqash et al 1 reported major adverse cardiac events (MACEs) with immune checkpoint inhibitors (ICI) through the clinical trial database of the National Cancer Institute (NCI). As underlined by the authors, ICI-related myocarditis is a rare but life-threatening immune-related adverse event, with little data about predictors of outcome. Importantly, if myocarditis accounted for 45% of ICI-related MACEs, ICI may be responsible for acute coronary syndrome, congestive heart failure, pericardial disease, dysrhythmia, and cardiac arrest. In this work, the report of nonmyocarditis MACE is of particular interest since previous studies mostly focused on ICI-related myocarditis. Furthermore, the authors noted that nonmyocarditis MACEs were more commonly reported when ICI were associated with targeted therapies, questioning the impact of these associations on microvasculature and atherosclerosis progression, as recently reported by others. 2 These observations

Comparison of clinical safety between standard versus extended interval dosing of immune checkpoint inhibitors: a real-world retrospective cohort study

“… 25 Another explanation may also lie in the common risk factors in patients with lung cancer who were prone to develop major cardiovascular adverse events or pulmonary hypertension following ICI treatment. 26 , 27 …”

Reply to S. Rossi et al and P. Palassin et al

“…These events are infrequent and thus such large population-level real-world databases can help in understanding toxicity trends and outcomes. 10 Palassin et al 2 ask if our review would suggest an under-reporting of these events. To that end, we wanted to highlight our rigorous methodology.…”

“…We thank both Rossi et al 1 and Palassin et al 2 for critically evaluating our recently published results 3 and providing additional insights on immune checkpoint inhibitor (ICI)–associated major adverse cardiac events (MACEs).…”

“…We thank Palassin et al 2 for highlighting the role of the pharmacovigilance databases, specifically VigiBase 9 in expanding on real-world immune toxicities, especially for MACE. These events are infrequent and thus such large population-level real-world databases can help in understanding toxicity trends and outcomes.…”