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Abstract
Background Immune checkpoint inhibitors (ICI) can cause a myriad of immune related complications, including myocarditis which has a mortality of 25 to 50%.1 The impact of peripheral cytokine levels on prognosis and treatment of ICI myocarditis has not been well described.
Methods This was a retrospective cohort of patients with ICI myocarditis treated at MD Anderson Cancer Center between January 2011 and May 2022. ICI myocarditis was defined by the adjudication criteria of myocarditis in the setting of cancer therapeutics.2 Cytokine levels were obtained during the index hospitalization with ICI myocarditis and measured by two clinical laboratory improvement amendments (CLIA)-certified assays. If cytokine levels were measured more than once, the peak value was used. Major adverse cardiovascular events (MACE) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis (myocardial infarction, stroke, lower limb ischemia), life-threatening arrhythmias (asystole, pulseless electrical activity, third degree heart block, sustained ventricular tachycardia, ventricular fibrillation), pulmonary embolism, and sudden cardiac death. Kaplan Meier curves for MACE free and all-cause mortality with censoring at 90 days and log rank test for comparing survival were used.
Results Ninety-nine patients were identified with ICI myocarditis. The mean age was 67.8 ± 12.7 years and majority were male (70%) and Caucasian (83%). The most common cancer groups were genitourinary (32%), melanoma (22%), and lung (17%). MACE occurred in 13% of patients with the most common being heart failure (62%), life threatening arrhythmia (38%), and sudden cardiac death (31%). Tumor necrosis factor-α (TNF-α), Interferon γ (IFN-γ), and Interleukin (IL)-6 were checked in 65 of the 99 patients. TNF-α and IL-6 were elevated in 69% and 82% of patients, respectively. IFN-γ was elevated in 31% of patients. Other cytokine levels were elevated in less than 20% of patients, except for IL2 receptor at 62% (table 1). MACE and overall mortality of patients with TNF-α levels above the median level of 32.5 pg/mL was higher compared to those with TNF-α in the lower 50% percentile (p-value 0.031) (figure 1). The administration of infliximab showed similar MACE free and overall survival between all patients and those with elevated TNF-α (p-value 0.698 and 0.830 respectively).
Conclusions Elevated TNF-α may be a sign of worse prognosis in patients with ICI myocarditis. However, the selective use of infliximab in this patient group did not improve outcomes. Therefore, peripheral cytokine levels may aid in prognostication but their use to guide myocarditis therapy is limited.
References
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Bonaca MP, Olenchock BA, Salem JE, Wiviott SD, Ederhy S, Cohen A, Stewart GC, Choueiri TK, Di Carli M, Allenbach Y, Kumbhani DJ, Heinzerling L, Amiri-Kordestani L, Lyon AR, Thavendiranathan P, Padera R, Lichtman A, Liu PP, Johnson DB, Moslehi J. Myocarditis in the setting of cancer therapeutics: proposed case definitions for emerging clinical syndromes in cardio-oncology. Circulation. 2019;140(2):80–91. doi: 10.1161/CIRCULATIONAHA.118.034497. PMID: 31390169; PMCID: PMC6779326.
Ethics Approval This study was approved by the institutional review board 4.
Consent A waiver of informed consent was provided by the institutional review board for this retrospective chart review study.
Cytokine Levels in Patients with Immune Checkpoint Inhibitor Myocarditis
Kaplan Meier Curves of Major Adverse Cardiovascular Event Free and Overall Survival