Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series
Cyrille Coustal, Juliette Vanoverschelde, Xavier Quantin, C. Lesage, Jean‐Marie Michot, Ariane Lappara, Stéphane Éderhy, Eric Assénat, Maxime Faure, Nahéma Issa, Olivier Lambotte, Mathieu Puyade, O. Dereure, Diégo Tosi, P. Rullier, Isabelle Serre, Romaric Larcher, Kada Klouche, Gérald Chanques, Hélène Vernhet‐Kovacsik, Jean‐Luc Faillie, Audrey Agullo, François Roubille, Philippe Guilpain, A. Maria
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.