Incidence, Clinical Characteristics, and Predictors of Cardiovascular Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors

Abstract

Background Cardiovascular immune-related adverse events (CV–irAEs) associated with immune checkpoint inhibitors (ICIs) may have been underreported given that most previous reports were retrospective. We aimed to evaluate the incidence, clinical characteristics, and predictors of CV–irAEs and determine the feasibility of serial cardiac monitoring using a combination of B-type natriuretic peptide, cardiac troponin T, and electrocardiogram for the prediction of future symptomatic (grade ≥2) CV–irAEs. Materials and Methods This was a prospective observational study that included 129 consecutive patients with non–small-cell lung cancer who received ICI monotherapy at a single center. Serial cardiac monitoring was performed during ICI monotherapy. Results A total of 35 (27%) patients developed any grade ≥1 CV–irAEs with a median time of onset of 72 (interquartile range 44-216) days after ICI treatment initiation. Multivariate Fine–Gray regression analysis showed that prior acute coronary syndrome (adjusted hazard ratio [HR] 3.15 (95% [CI], 2.03-4.91), prior heart failure hospitalization (adjusted HR 1.65 [95% CI, 1.17-2.33]), and achievement of disease control (adjusted HR 1.91, [95% CI, 1.16-3.14]) were significantly associated with grade ≥1 CV–irAEs. Serial cardiac monitoring revealed that patients with preceding grade 1 CV–irAEs were associated with a significantly higher risk of onset of grade ≥2 CV–irAEs compared with those without preceding grade 1 CV–irAEs (HR: 6.17 [95% CI, 2.97-12.83]). Conclusion CV–irAEs were more common than previously recognized and have several predictors. Moreover, serial cardiac monitoring may be feasible for the prediction of future grade ≥2 CV–irAEs.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

“…Patients with non-small-cell lung cancer, receiving ICI monotherapy, were investigated by Isawa et al in a prospective observational study [57]. One hundred and twenty-nine patients were enrolled and received serial cardiac monitoring, i.e., hs-TnT, BNP, and an ECG at baseline and every four to six weeks thereafter.…”

Multidisciplinary recommendations for essential baseline functional and laboratory tests to facilitate early diagnosis and management of immune-related adverse events among cancer patients

“…If results are normal, these tests can be spaced to every three doses [43][44][45]. It is worth mentioning that troponin I and T are not expressed in the skeletal muscle of healthy adult patients, but troponin T is found within the fetal skeletal muscle.…”

“…We suggest performing a clinical evaluation, an electrocardiogram, a measurement of serum troponin T and, where available, a troponin I at baseline in all patients prior to ICI treatment initiation and up to the 4th administration. If results are normal, these tests can be spaced to every three doses [ 43 – 45 ]. It is worth mentioning that troponin I and T are not expressed in the skeletal muscle of healthy adult patients, but troponin T is found within the fetal skeletal muscle.…”

ANGPTL2 promotes immune checkpoint inhibitor-related murine autoimmune myocarditis

“…A study of data from eight clinical sites showed myocarditis prevalence to be 1.14% after ICI treatment, with a median time of onset of 34 days after starting ICIs 5 . However, a recent study suggested that cardiac irAEs may be underreported due to failure to diagnose asymptomatic cases 6 . Of note, the mortality rate of ICI-related myocarditis is reportedly as high as 50% 7 .…”