Immune-Checkpoint Inhibitor-Induced Fulminant Myocarditis and Cardiogenic Shock

Immune checkpoint inhibitor-induced myocarditis in cancer patients: a case report and review of reported cases

“…Surveillance CT showed tumor control [ 17 ]. These findings could suggest that treatment with alemtuzumab or abatacept as second line therapy could be effective in treating ICI-induced myocarditis as both substances target T-lymphocytes, which are the predominant finding in endomyocardial biopsies from patients with ICI-induced myocarditis, as reported in both this and previous studies [ 11 , 16 , 19 , 22 , 23 , 26 , 36 – 39 , 42 , 43 , 47 , 50 , 61 , 62 , 67 , 71 ]. Furthermore treating ICI-induced myocarditis with alemtuzumab or abatacept could have a positive outcome in regard to tumor control compared to other immunosuppressive agents.…”

“…The diagnosis of myocarditis was based on cardiac biomarkers, ECG, echocardiography, cardiac magnetic resonance or computer tomography of the heart, cardiac catherization and endomyocardial biopsy. Twenty studies included biopsy-verified myocarditis with findings of immune infiltration of the myocardium with CD4-positive T-lymphocytes, CD8-positive T-lymphocytes and CD68-positive macrophages [ 11 , 16 , 19 , 22 , 23 , 26 , 36 – 39 , 42 , 43 , 47 , 50 , 61 , 62 , 67 , 71 ]. One study included several biopsies performed during and after immunosuppressive therapy showing improvement with evidence of early repair, less inflammatory cells and patchy foci of fibrosis [ 22 ].…”

“… [ 16 , 22 , 26 , 49 , 56 , 57 , 64 , 67 ] (total: 11) Mycophenolate mofetil Inhibits the proliferation of T- and B-lymphocytes Has a cytostatic effect on B- and T-lymphocytes Risk of infections. Risk of reactivating hepatitis B or C, Epstein-Barr virus and Cytomegalovirus [ 8 , 15 , 17 , 21 , 22 , 26 , 35 , 54 , 57 , 64 , 68 ] (total: 14) Infliximab Monoclonal antibody inhibits tumor necrosis factor (TNF-alfa) Inhibits cell signaling that induces inflammation Risk of serious infections [ 18 , 39 , 47 , 50 , 56 , 57 , 62 , 65 ] (total: 8) Alemtuzumab Monoclonal antibody that binds to CD52 on the surface of mature T- and B-lymphocytes, which induces their destruction through activation of the complement system Induces rapid T-cell depletion Risk of inducing autoimmune diseases and infections [ 8 ] (total: 1) Abatacept A fusion protein that binds CD28/CD86, which modulates the co-stimulation of T-cells so they cannot be activated Blocks the activation of T-cells Risk of infections, risk of inducing malignancy [ …”

“…The immunosuppressive therapy regimens in the cases treated with immunosuppressive agents other than steroid (23 out of 49) varied, as only 3 cases were not treated with steroid initially, but with only one immunosuppressive agent being either ATG (1 patient) [ 67 ] or immunoglobulin (3 patients) [ 53 ]. The other 20 cases were treated with steroid initially, followed by one to four other immunosuppressive agents due to lack of improvement in clinical condition, cardiac biomarkers, ECG or LVEF [ 7 – 9 , 15 , 17 – 20 , 22 , 26 , 34 , 35 , 41 , 42 , 54 , 56 , 58 , 69 , 70 ].…”

Preventive Cardio-Oncology: The Time Has Come

“…Various forms of early toxicity may be more likely to show up on some modalities than others (black arrows, Figure 1F). For example, most groups recommend ECG and troponin for monitoring of early toxicity from immune checkpoint inhibitors, of course along with observation for symptoms and assessment of vitals; with escalation to cardiac MRI if suspicion for myocarditis persists, or endomyocardial biopsy, if indicated, in conjunction with Cardio-Oncology consultation and management (13,(160)(161)(162)(163). Weekly monitoring of troponin may be pursued for the first 6 weeks, given that aggressive and often fulminant myocarditis typically occurs at a median of 30 days from initiation of therapy (13,164).…”