A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors

Jessica Castrillon Lal,Feixiong Cheng,Patrick Collier,Sherry-Ann Brown

doi:10.1186/s40959-021-00106-x

Abstract

BackgroundModern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported.MethodsWe performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010–March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy.ResultsWe found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76–48.42, (adjusted p-value) q < 0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03–51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37–0.69, q < 0.001), CTLA4, OR = 0.08 (95% CI 0.03–0.20, q < 0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13–0.48, q < 0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75–0.87, q < 0.001), coronary artery disease, 0.63 (95% CI 0.53–0.76, q < 0.001), myocardial infarction, OR = 0.60 (95% CI 0.53–0.67, q < 0.001), myocarditis, OR = 0.59 (95% CI 0.47–0.75, q < 0.001) and pericarditis, OR = 0.5 (95% CI 0.35–0.73, q < 0.001).ConclusionOur study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.

Highlights

Immune checkpoint inhibitors (ICIs) have increased cancer survivorship and are standard of care for numerous cancer types [1,2,3]
Elevated cardiovascular risk of immune checkpoint inhibitors To evaluate the frequency of cardiac adverse events in patients treated with ICIs compared to classical chemotherapy, we performed a retrospective analysis using the FDA Adverse Event Reporting System
All adverse events case reports for anti-PD1, anti-program death ligand 1 (PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapies, and classical chemotherapy agents were extracted in July 2020 (Additional File 1: Supplemental Table 2)

Summary

Introduction

Immune checkpoint inhibitors (ICIs) have increased cancer survivorship and are standard of care for numerous cancer types [1,2,3]. All patients receiving more than one ICI experience adverse events (90%) [6]. While cardiac adverse events comprise less than 1% of all AE, they are disproportionally more lethal [6]. It is unclear whether this low incidence results from a lack of reporting or misdiagnosis in part due to heterogeneity in clinical presentation. Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported

Methods

Results

Discussion

Conclusion