Clatterbridge Cancer Centre, Liverpool, United Kingdom
Alexandra Johnson , Adam Chapman , Nicholas Garbutt , Richard Griffiths , Anthony Pope , Anna Claire Olsson-Brown
Background: As a large regional tertiary cancer centre with an established cardio-oncology service a high incidence immune checkpoint inhibitor (ICI) induced myocarditis was recognised in mesothelioma patients receiving combination ICIs (cICI). A retrospective analysis of myocarditis in patients with mesothelioma was conducted. The utility of baseline cardiac markers as a prospective stratification tool for the development of ICI induced myocarditis in this patient group was investigated. Methods: A retrospective analysis of 118 patients with mesothelioma treated with ICIs over a 5 year period at the Clatterbridge Cancer Centre, Liverpool, UK. Baseline characteristics, treatment regimen, co-morbidities and the presence of malignant pericardial or cardiac disease were recorded. Baseline cardiac markers (high sensitivity Troponin T (hsTT) and pro-BNP) were recorded for patients initiating ICI treatment from July 2022 when regional baseline testing was introduced. A diagnosis of myocarditis was confirmed by cardiac MRI (n = 6) or clinically by the cardio-oncology team when MRI was clinically unfeasible (n = 1). Statistical analysis was undertaken with Fishers Exact test. Results: 33 patients received cICI treatment with Ipilimumab and Nivolumab, 85 patients received monotherapy ICIs (mICI), 5 as a SACT combination. Myocarditis occurred in 12.1% (n = 4) of patients receiving cICIs vs 3.5% (n = 3) of patients receiving mICIs. The median onset was 57 days with cICI and 245 days with mICI treatment. Baseline (b/l) cardiac assessment was undertaken in 22 patients (66.7%) of those treated with cICIs and 8 patients (9.4%) treated with mICI therapy. An abnormal b/l pro-BNP ( > 500 ng/L) was identified in 5 cICI patients and 1 mICI patient. Those with elevated b/l pro-BNP in the cICI setting all had a significant cardiac association; either an increased incidence of myocarditis (n = 3/5) (p = 0.0065) or pericardial/ invasive cardiac disease (n = 2/5) (p = 0.0433). In the cICI population myocarditis was not seen in patients with a b/l pro-BNP < 500ng/L. Of the 8 mICI patients with b/l cardiac assessment, 1 patient had an elevated pro-BNP which was associated with pericardial extension. Regarding baseline hsTT in the cICI group, the incidence of myocarditis was not increased with mild b/l elevations (14-24 ng/L), however, a moderately elevated level ( > 24ng/L) was associated with an increased incidence of myocarditis (p = 0.0026). Conclusions: In this cohort of patients with mesothelioma there was a high incidence of cICI induced myocarditis. As patients treated with cICIs with abnormal b/l cardiac markers had an increased risk of developing ICI induced myocarditis, b/l cardiac markers could potentially be used to help stratify the risk of ICI induced myocarditis and inform treatment discussions. Further studies are now required.
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