Characterization of Immune Checkpoint Inhibitor-Related Cardiotoxicity in Lung Cancer Patients From a Rural Setting

Melissa Y Y Moey; Anna N Tomdio; Justin D McCallen; Lauren M Vaughan; Kevin O'Brien; Abdul R Naqash; Cynthia Cherry; Paul R Walker; Blase A Carabello

doi:10.1016/j.jaccao.2020.07.005

Characterization of Immune Checkpoint Inhibitor-Related Cardiotoxicity in Lung Cancer Patients From a Rural Setting

JACC CardioOncol. 2020 Sep 15;2(3):491-502. doi: 10.1016/j.jaccao.2020.07.005. eCollection 2020 Sep.

Authors

Melissa Y Y Moey¹, Anna N Tomdio², Justin D McCallen³, Lauren M Vaughan⁴, Kevin O'Brien⁵, Abdul R Naqash^{6

7}, Cynthia Cherry⁶, Paul R Walker⁶, Blase A Carabello¹

Affiliations

¹ Department of Cardiovascular Sciences, Vidant Medical Center, East Carolina University, Greenville, North Carolina, USA.
² Department of Cardiovascular Sciences, Virginia Commonwealth University, Richmond, Virginia, USA.
³ Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
⁴ Department of Internal Medicine, Vidant Medical Center, East Carolina University, Greenville, North Carolina, USA.
⁵ Department of Biostatistics, East Carolina University, Greenville, North Carolina, USA.
⁶ Department of Hematology and Oncology, Vidant Medical Center, East Carolina University, Greenville, North Carolina, USA.
⁷ U.S. National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Background: Immune checkpoint inhibitor (ICI)-related cardiotoxicity (iRC) is uncommon but can be fatal. There have been few reports of iRC from a rural cancer population and few data for iRC and inflammatory biomarkers.

Objectives: The purpose of this study was to characterize major adverse cardiac events (MACE) in ICI-treated lung cancer patients based in a rural setting and to assess the utility of C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) in the diagnosis of iRC.

Methods: Patients with lung cancer treated with ICIs at Vidant Medical Center/East Carolina University (VMC/ECU) between 2015 and 2018 were retrospectively identified. MACE included myocarditis, non-ST-segment elevated myocardial infarction (NSTEMI), supraventricular tachycardia (SVT), and pericardial disorders. Medical history, laboratory values, pre-ICI electrocardiography (ECG), and echocardiography results were compared in patients with and without MACE.

Results: Among 196 ICI-treated patients, 23 patients (11%) developed MACE at a median of 46 days from the first ICI infusion (interquartile range [IQR]: 17 to 83 days). Patients who developed MACE experienced myocarditis (n = 9), NSTEMI (n = 3), SVT (n = 7), and pericardial disorders (n = 4). Ejection fraction was not significantly different at the time of MACE compared to that at baseline (p = 0.495). Compared to baseline values, NLR (10.9 ± 8.3 vs. 20.7 ± 4.2, respectively; p = 0.032) and CRP (42.1 ± 10.1 mg/l vs. 109.9 ± 15.6 mg/l, respectively; p = 0.010) were significantly elevated at the time of MACE.

Conclusions: NLR and CRP were significantly elevated at the time of MACE compared to baseline values in ICI-treated patients. Larger datasets are needed to validate these findings and identify predictors of MACE that can be used in the diagnosis and management of ICI-related iRC.

Keywords: CAR T, chimeric antigen receptor T cell; CTCAE, common terminology for clinical adverse events; CTLA-4, cytotoxicity T-cell lymphocyte antigen; ICI, immune checkpoint inhibitor; MACE, major adverse cardiac events; NLR, neutrophil-to-lymphocyte ratio; NSCLC, non-small cell lung cancer; PD, programmed cell death; PD-L1, programmed cell death-ligand 1; iRC, immune checkpoint inhibitor-related cardiotoxicity; immune checkpoint inhibitors; inflammatory markers; irAE, immune-related adverse events; myocarditis; neutrophil-to-lymphocyte ratio.