Successful treatment of immune checkpoint inhibitor-associated fulminant myocarditis with abatacept and ruxolitinib: a case report
Abstract
Abstract Background Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy with growing indications for treatment of various malignancies. Immune checkpoint inhibitors are monoclonal antibodies that block inhibitory pathways in immune cells, including cytotoxic T lymphocyte antigen-4 (CTLA4), programmed death 1 receptor (PD1), and programmed cell death ligand-1 (PDL1), to activate the immune system. However, these agents can disrupt self-tolerance and lead to immune-related adverse events. Fulminant myocarditis, a feared complication of ICIs, can be highly fatal, and there is a need for effective treatment options. Case summary A 70-year-old patient with recurrent metastatic disease of urothelial carcinoma subsequently developed fulminant myocarditis after receiving eight cycles of pembrolizumab. He developed cardiogenic shock and required inotropes and a percutaneous microaxial flow pump placement for temporary mechanical circulatory support. He received methylprednisolone initially and then was started on second-line immunosuppression agents, ruxolitinib and abatacept, for steroid-refractory myocarditis. Abatacept is thought to inhibit activation of T-cell CTLA4 and PD1/PDL1 pathways and reverse ICI-activated pathways. Ruxolitinib is a Janus kinase inhibitor that impairs immune activation through suppressing cytokine sensing and production and T-cell activation. After these treatments, the patient subsequently clinically improved and his myocarditis…
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