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.

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Naqash et al 1 reported major adverse cardiac events (MACEs) with immune checkpoint inhibitors (ICI) through the clinical trial database of the National Cancer Institute (NCI). As underlined by the authors, ICI-related myocarditis is a rare but life-threatening immune-related adverse event, with little data about predictors of outcome. Importantly, if myocarditis accounted for 45% of ICI-related MACEs, ICI may be responsible for acute coronary syndrome, congestive heart failure, pericardial disease, dysrhythmia, and cardiac arrest. In this work, the report of nonmyocarditis MACE is of particular interest since previous studies mostly focused on ICI-related myocarditis. Furthermore, the authors noted that nonmyocarditis MACEs were more commonly reported when ICI were associated with targeted therapies, questioning the impact of these associations on microvasculature and atherosclerosis progression, as recently reported by others. 2 These observations

Background and Objectives:CTLA4 deficiency (CTLA4d) is a disease with multisystem auto-immune features, including neurological manifestations. We aimed to describe neurological involvement in these patients.Methods:We performed a cross-sectional observational study using the French Reference Centre for Primary Immunodeficiencies (CEREDIH) registry, plus a surveillance in national society networks. Participants with confirmed CTLA4d and neurological involvement were included. Clinical, laboratory and radiological features were collected, as well as treatments. Available MRI were double-reviewed.Results:Among 70 patients with CTLA4d, 13 patients (21%) had neurological involvement. Neurological symptoms began at a median age of 18 [15-45] years, mostly occurring after systemic manifestations (median delay: 8.5 [4.5-10.5] years). Main symptoms included headaches, focal deficit (54% each) and seizures (38%). MRI detected at least one large contrast-enhancing lesion in eight patients. Lesions reminiscent of multiple sclerosis lesions were found in six patients. Cerebellar (6 patients) and large spinal cord lesions (3 patients) were common. Ten patients were treated with Abatacept, of whom nine (90%) showed good clinical and radiological response.Discussion:Neurologic involvement is common among patients with CTLA4d. Despite its rarity, and considering the suspected efficacy of Abatacept, neurologists should be aware of the characteristics of CTLA4d neurological involvement.

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