Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series

Abstract

BackgroundImmune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening.MethodsWe conducted a multicenter cross-sectional retrospective study with the aim of better characterizing ICI-related myocarditis. Myocarditis diagnosis was based on the recent consensus statement of the International Cardio-Oncology Society.ResultsTwenty-nine patients were identified, from six different referral centers. Most patients (55%) were treated using anti-programmed-death 1, rather than ICI combination (35%) or anti-programmed-death-ligand 1 (10%). Transthoracic echocardiography was abnormal in 52% of them, and cardiac magnetic resonance showed abnormal features in 14/24 patients (58%). Eleven patients (38%) were classified as severe. Compared with other patients, they had more frequently pre-existing systemic autoimmune disease (45% vs 6%, p=0.018), higher troponin level on admission (42-fold the upper limit vs 3.55-fold, p=0.001), and exhibited anti-acetylcholine receptor autoantibodies (p=0.001). Seven patients (24%) had myocarditis-related death, and eight more patients died from cancer progression during follow-up. Twenty-eight patients received glucocorticoids, 10 underwent plasma exchanges, 8 received intravenous immunoglobulins, and 5 other immunosuppressants. ICI rechallenge was performed in six patients, with only one myocarditis relapse.DiscussionThe management of ICI-related myocarditis may be challenging and requires a multidisciplinary approach. Prognostic features are herein described and may help to allow ICI rechallenge for some patients with smoldering presentation, after an accurate evaluation of benefit–risk balance.

Underreporting of Major Cardiac Adverse Events With Immune Checkpoint Inhibitors in Clinical Trials: Importance of Postmarketing Pharmacovigilance Surveys

“…Finally, the fatality rate reported by Naqash et al 1 is lower than early reports (22.5% v 50%) but close to recent publications including our own series of 29 ICI-related myocarditis 9 and data from VigiBase. Beyond progresses made in early detection of ICI-related MACE, there also may be smoldering cases who benefit from early steroid treatment, the main prognostic factor of outcome to date.…”

“…In our experience, six patients were successfully rechallenged after ICI-related MACE, with only one myocarditis relapse with favorable outcome. 9 Altogether, the study by Naqash et al, The same report can be reported with more than one reporter qualification.…”

“…In our experience, six patients were successfully rechallenged after ICI-related MACE, with only one myocarditis relapse with favorable outcome. 9…”

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study

“…Coustal et al. 17 found that the median time to the onset of myocarditis was 39 days. A retrospective pooled analysis including 18 myocarditis patients showed that patients exhibited myocarditis following a median of two administrations of ICI (with an IQR of 1–3.5 doses), and this occurred at a median of 35 days (with an IQR of 19–80 days) after the initial administration of ICIs.…”

Severe acute myositis and myocarditis upon initiation of six-weekly Pembrolizumab post-COVID-19 mRNA vaccination

“…Pharmacovigilance studies of immunotherapy associated myocarditis show a higher incidence and increased severity in recipients of combination anti-CTLA-4 and anti-PD-1 immunotherapy, whilst approximately 25% of cases show evidence of myositis and 10% have features of myaesthenia gravis 19 . Occurrence of all three is referred to as the '3M syndrome', has a much lower incidence than myocarditis alone, and is more severe 20 . Strikingly, all three described cases had characteristics of the '3M' syndrome.…”