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

Abstract

Background: Immune 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.

Methods: We 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.

Results: Twenty-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.

Discussion: The 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.

Keywords: Immunotherapy; Lung Neoplasms; Melanoma; Programmed Cell Death 1 Receptor.

Figure 1

Time from immune checkpoint inhibitor initiation to myocarditis occurrence (days, median, IQR and min–max).

Figure 2

Cardiac MRI demonstrating myocardial inflammation in a 33-year-old woman. (A) Short-axis-native T1 map showing elevated signal (1246±108 ms) consistent with hyperemia and/or fibrosis. (B) Vertical-long-axis Short Tau Inversion Recovery (STIR) image showing midventricular and basal edema. (C, D) Short-axis late enhancement images showing subepicardial late gadolinium enhancement consistent with fibrosis and necrosis in mid and basal left ventricular cardiac wall.

Figure 3

Receiver operating characteristic curve for admission troponin between severe and non-severe patients.