Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy

Abstract

Background:Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality.Methods:In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids.Results:This report describes the only case of immune-mediated myocarditis treated with ATGAM resulting in a favourable outcome.Conclusions:Use of ATGAM should be considered in cases of steroid-refractory immune-mediated myocarditis and administered in close consultation with a cardiac transplant team experienced in the use of this agent.

Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action

“…The first specific report of myocarditis during treatment with a PD‐1/PD‐L1 inhibitor was published in 2014 [27], and a number of cases of ICI‐associated myocarditis have been described since . In an early analysis of more than 20,000 patients treated with ICIs, either alone or in combination, the incidence of myocarditis was 0.09%; the incidence of fatal myocarditis in this sample was 0.03% .…”

“…There are no universally accepted criteria for a diagnosis of ICI‐associated myocarditis, but position statements and clinical practice guidelines for myocarditis due to other causes provide benchmarks. Inexpensive and widely available tests used for diagnosing ICI‐associated myocarditis include troponin measurements and electrocardiograms . However, these tests lack the sensitivity and specificity for a definitive myocarditis diagnosis.…”

“…Additional standard imaging methods that have been used for the assessment and diagnosis of ICI‐associated myocarditis include echocardiography and cardiac magnetic resonance imaging, which may reveal left‐ventricular ejection fraction abnormalities, wall motion abnormalities, myocardial edema, and fibrosis. Even endomyocardial biopsy, currently considered the gold‐standard method for diagnosis, has its limitations, as ICI‐associated myocarditis may occur as a patchy distribution of T‐cell‐predominant lymphocytic infiltrate within or adjacent to regions of myocardial necrosis , similar to histologic findings in patients with cardiac transplant rejection . Therefore, proper diagnosis of ICI‐associated myocarditis may involve a combination of high clinical acumen, biomarkers, cardiac imaging, and endomyocardial biopsy.…”

New drugs and new toxicities: pembrolizumab-induced myocarditis

“…ACE inhibitors can be employed to decrease heart failure-related morbidity and mortality 22. A rapid recovery is usually observed with the corticosteroid treatment 23. However, the use of equine antithymocyte globulin may be considered in steroid non-responders 23.…”

“…A rapid recovery is usually observed with the corticosteroid treatment 23. However, the use of equine antithymocyte globulin may be considered in steroid non-responders 23. Pembrolizumab therapy should be halted and an alternative antitumour treatment must be sought out to avoid immune-mediated myocarditis in such patients.…”