Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor-Induced Myocarditis.
ALT
ALT, alanine aminotransferase
AST
AST, aspartate aminotransferase
CPK
CPK, creatine phosphokinase
ICI, immune checkpoint inhibitor
LDH, lactate dehydrogenase
ULN, upper limit of normal
biomarkers
hsTnT, high-sensitivity troponin T
immune checkpoint inhibitor
immunotherapy
irAE, immune-related adverse event
myocarditis
troponin
Journal
JACC. CardioOncology
ISSN: 2666-0873
Titre abrégé: JACC CardioOncol
Pays: United States
ID NLM: 101761697
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
01
06
2022
revised:
02
11
2022
accepted:
04
11
2022
entrez:
13
1
2023
pubmed:
14
1
2023
medline:
14
1
2023
Statut:
epublish
Résumé
Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis. The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes. We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy. Among 2,606 patients (mean age 64 ± 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis. ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis.
Sections du résumé
Background
UNASSIGNED
Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis.
Objectives
UNASSIGNED
The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes.
Methods
UNASSIGNED
We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy.
Results
UNASSIGNED
Among 2,606 patients (mean age 64 ± 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis.
Conclusions
UNASSIGNED
ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis.
Identifiants
pubmed: 36636441
doi: 10.1016/j.jaccao.2022.11.004
pii: S2666-0873(22)00459-8
pmc: PMC9830199
doi:
Types de publication
Journal Article
Langues
eng
Pagination
689-700Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007853
Pays : United States
Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
Dr Vasbinder is supported by a National Heart, Lung, and Blood Institute funded postdoctoral fellowship (T32HL007853). Dr Hayek is supported by National Heart, Lung, and Blood Institute (R01HL153384) and the National Institute on Diabetes and Digestive and Kidney Diseases (R01-DK128012). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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