Abstract 12324: Biomarker Trends in Patients With Immune-Checkpoint Inhibitor Myocarditis

Introduction: Immune checkpoint inhibitors (ICIs) are associated with myocarditis; however, there is no consensus on strategies to identify or monitor for myocarditis. We sought to characterize longitudinal biomarkers in patients receiving ICIs. Methods: We conducted an observational cohort study of adult (≥18 years) patients who had received at least one dose of single or dual ICI at Michigan Medicine between June 2014 - December 2021. Patients were identified as having myocarditis if a clinical diagnosis was noted in the medical record by the cardiovascular consult team. Laboratory values (i.e., high-sensitivity troponin-T [hsTnT], aspartate transaminase [AST], alanine transaminase [ALT], lactate dehydrogenase [LDH], and creatinine phosphokinase [CPK]) were collected from medical records for 12 months after beginning ICI. Results: In 2,606 patients (mean (SD) age 64 (13) years; 60.8% male), 27 (1.0%) developed myocarditis at a median (IQR) time of 28 (18,40) days after starting ICIs. At diagnosis, most patients with myocarditis had a non-cardiac immune-related adverse event (88.9%) and an elevated ALT (88.9%), AST (85.2%), CPK (88.9%), and LDH (92.6%). All patients with myocarditis had an elevated hsTnT. Compared to patients without myocarditis, patients with myocarditis had significant elevations in ALT, AST, CPK, and LDH after starting ICIs (all P<0.001) (Figure). In patients with myocarditis, average concentrations of AST and ALT remained elevated at 12 months, whereas CPK peaked at 1 month then rapidly declined. Average concentrations of all biomarkers in patients without myocarditis were in the normal range. CPK values greater than the upper limit of normal had a sensitivity and specificity of detecting myocarditis of 99% and 23%, respectively. Conclusions: Myocarditis rarely occurs in the absence of other immune-related adverse events. Elevated AST, ALT and CPK should prompt measuring hs-TnT and initiating further evaluation for ICI myocarditis.