Prior acute coronary syndrome, prior heart failure hospitalization, and achievement of disease control were significantly associated with cardiovascular immune-related adverse events (CV-irAEs) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Preceding low-grade CV-irAEs also are associated with increased risk of developing higher grade CV-irAEs. These findings were published in The Oncologist.
Concern about potential underdiagnosis and underreporting of CV-irAEs in patients treated with ICIs prompted a retrospective observational study to determine the incidence and predictors of CV-irAEs, as well as clinical characteristics. The study also sought to determine whether cardiac monitoring was a feasible predictor of worsening CV-irAEs.
For this study, 129 consecutive patients with non-small cell lung cancer (NSCLC) who received ICI monotherapy were recruited for a single-center registry. Serial cardiac monitoring using a combination of B-type naturiuretic peptide (BNP), cardiac troponin T, and electrocardiography (ECG) were used for early detection of future symptomatic CV-irAEs. All patients agreed to participate, and all underwent cardiac monitoring.
A total of 35 patients developed any grade 1 (asymptomatic) or higher CV-irAEs; median time to onset was 72 days (IQR 44 to 216) after initiation of ICI therapy. Thirteen patients developed any grade 2 (symptomatic) or higher CV-irAE, with 6 of them (46%) having experienced a preceding grade 1 CV-irAE prior to its onset. Median time to onset of grade 2 or higher CV-irAE was 141 days (IQR, 69 to 234) after initiation of ICI therapy.
Prognostic factors found to significantly associate with grade 1 or higher CV-irAEs were prior acute coronary syndrome, prior heart failure hospitalization, and achieving disease control (adjusted hazard ratio [HR], 3.15, 1.65, and 1.91, respectively). Prognostic factors for grade 2 or higher CV-irAEs were performance status 2 or higher and achieving disease control.
Serial cardiac monitoring showed patients with preceding grade 1 CV-irAEs were at significantly higher risk of developing grade 2 or higher CV-irAES, compared with patients without preceding grade 1 CV-irAEs (HR, 6.17; 95% CI, 2.97-12.83).
Data analyzed were from patients with NSCLC; therefore, study results may not be generalizable to patients with other types of cancer. Other study limitations included lack of a control group, quantitative troponin T or I data were not obtained, and laboratory tests and ECG data were only collected at every other ICI treatment cycle, so some events may have been missed in the interim.
Future studies should investigate serial cardiac monitoring for patients undergoing dual ICI therapy, as these patients appear to experience severe myocarditis more frequently than do patients treated with ICI monotherapy alone.
Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Isawa T, Toi Y, Sugawara S, Taguri M, Toyoda S. Incidence, clinical characteristics, and predictors of cardiovascular immune-related adverse events associated with immune checkpoint inhibitors. Oncologist. March 28, 2022. doi:10.1093/oncolo/oyac056