Cardiac MRI study of adverse events in patients treated with immune checkpoint inhibitors: a prospective cohort study of cardiac adverse events

Abstract

Immune checkpoint inhibitors (ICIs) revolutionized cancer therapy, yet require management of immune-related adverse events (irAEs). Fulminant myocarditis is a rare irAE, but lower-severity cardiac events are being reported more frequently, leading to an unmet need for irAE prevention, early diagnosis, and treatment, especially for long-life-expectancy patients. We recruited 57 patients, stratified according to therapy regime (monotherapy (30%) or combination (33%) cohort) or history of cardiac disease or presence of at least two cardiovascular risk factors other than prior or active smoking (cardiovascular cohort (37%)). We performed a complete cardiological assessment with clinical visit, 12-lead ECG, multiparametric cardiac MRI as well as peripheral blood mononuclear cell immunophenotyping, prior to ICI initiation and around 2 months later. ICI treatment was associated with a significant left ventricular ejection function (LVEF) reduction pre-ICI versus post-ICI treatment (60.1±8% to 58.1±8%, p=0.002, paired t-test) and more than 3% LVEF loss in a substantial proportion of patients (18; 32%). These patients also showed significantly higher T2 values (p=0.037, unpaired t-test), putative sign of cardiac edema. The loss of cardiac function did not differ among patients with different tumor types, therapy regimes or history of cardiac disease. Immunophenotyping analyses showed a reduction of programmed cell death protein 1 staining on both CD4⁺ and CD8⁺ T cells, and an upregulation of HLA-DR on CD8⁺ T cells. Using a very sensitive and comprehensive approach in patients unselected for cardiac history, we found a subclinical but significant LVEF decrease. These findings may inform ongoing discussions on optimal management of cardiac irAEs in patients undergoing ICI treatment and warrant further evaluation.

Keywords: Cardiotoxicity; Immune Checkpoint Inhibitors; Immune related adverse event - irAE.