Blood-based biomarkers linked to immune checkpoint inhibitor-induced myocarditis
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Key findings:
- Patients with cancer and immune checkpoint inhibitor-induced myocarditis had early signs of liver damage and muscle injury.
- The results reveal the potential benefits of routine monitoring for immune-related adverse effects using creatine phosphokinase levels.
Most patients with cancer diagnosed with myocarditis after receiving immune checkpoint inhibitors showed evidence of liver dysfunction and muscle degradation, results of an observational cohort study in JACC CardioOncology showed.
Researchers observed a significant association between elevated creatine phosphokinase levels — a routinely collected noncardiac blood-based biomarker — and increased risk for immune checkpoint inhibitor-induced myocarditis.
“Immune checkpoint inhibitor-induced myocarditis can be very dangerous and should not be misdiagnosed given the implications surrounding cessation of cancer therapy and the consideration for heavy immunosuppression,” Salim S. Hayek, MD, medical director of the Frankel Cardiovascular Center at University of Michigan, told Healio. “These findings arm clinicians with an effective approach to recognize the complication and diagnose with higher confidence.”
Background
Myocarditis is a rare, deadly complication of immune checkpoint inhibitors, according to Hayek.
“Most patients present late, and when they do, they’re critically ill and can have up to a 50% chance of death,” he told Healio.
“Diagnosing immune checkpoint inhibitor-induced myocarditis is challenging, given there is no single test that can differentiate it from other causes of cardiac injury,” he added. “It is important to diagnose it fast, early and accurately in order to start immunosuppressive therapy as soon as possible.”
Hayek and colleagues conducted this study to determine whether routinely measured blood-based biomarkers could be used for earlier detection of myocarditis among patients who received immune checkpoint inhibitors.
Methodology
The investigators conducted an observational cohort analysis of 2,606 adults (mean age, 64 ± 13 years; 60.7% men) who received at least one dose of an immune checkpoint inhibitor at Michigan Medicine between June 2014 and December 2021.
The study included patients who underwent routine testing for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) while receiving an immune checkpoint inhibitor.
Researchers sought to identify any associations between measured biomarkers and incidence of immune checkpoint inhibitor-induced myocarditis and outcomes. They replicated their findings in an independent France-based cohort of 30 patients with biopsy-confirmed immune checkpoint inhibitor-induced myocarditis.
Results
Twenty-seven patients (1%) in the study cohort received a diagnosis of immune checkpoint inhibitor-induced myocarditis.
Biomarker analysis showed these patients had high levels of high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%) and LDH (92.6%).
Ninety-five percent of patients with immune checkpoint inhibitor-induced myocarditis showed elevations in at least three biomarkers compared with 5% of those who did not have myocarditis.
Multivariate analysis revealed CPK as the only noncardiac biomarker associated with increased hazard of developing immune checkpoint inhibitor-induced myocarditis (HR = 1.83; 95% CI, 1.59-2.1) and all-cause mortality (HR = 1.1; 95% CI, 1.01-1.2). CPK elevations had a 99% sensitivity and 23% specificity for identifying myocarditis.
Clinical implications
Many but not all centers that routinely prescribe immune checkpoint inhibitors as cancer treatment measure the biomarkers evaluated in this study as part of routine clinical care, according to Hayek. The results can help guide clinicians on screening and diagnosis for immune checkpoint inhibitor-induced myocarditis, he added.
“This study highlights the potential benefits of routinely monitoring for immune-related adverse effects using CPK levels,” he told Healio. “If myocardial injury occurs in the absence of a rise in CPK, then immune checkpoint-related myocarditis is highly unlikely.”
The small sample size serves as a crucial limitation to the study’s results, with 18 of the 27 patients included in the analysis having “possible” but not confirmed myocarditis, according to Allan S. Jaffe, MD, professor of medicine in the department of cardiovascular medicine and chair of the division of clinical core laboratory services at Mayo Clinic in Rochester, Minnesota.
In addition, the study did not have baseline biomarkers available for evaluation.
“It is known that a large percentage of patients with cancer will have baseline biomarker abnormalities,” he wrote in an accompanying editorial. “Thus, some of the increases potentially attributed to [immune checkpoint inhibitors] might be chronic ones. Whether these increases reflect prior disease or the direct effects of cancer biology on the cardiovascular system itself is unclear.”
References :
- Jaffe AS. J Am Coll Cardiol CardioOnc. 2022;doi:10.1016/j.jaccao.2022.11.014.
- Vasbinder A, et al. J Am Coll Cardiol CardioOnc. 2022;doi:10.1016/j.jaccao.2022.11.004.
For more information :
Salim Hayek, MD, can be reached at Department of Medicine, Division of Cardiology, University of Michigan Frankel Cardiovascular Center, 1500 E. Medical Center Drive, CVC #2709, Ann Arbor, MI 48109; email: shayek@med.umich.edu.
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