Case Report: Immune checkpoint inhibitor-associated myocarditis, myositis, and myasthenia gravis overlap syndrome with flow cytometric phenotyping before and after treatment in a patient with urothelial carcinoma

Immune checkpoint inhibitor-associated myocarditis, myositis, and myasthenia gravis overlap syndrome (IM3OS) is an uncommon immune-related adverse event (irAE) associated with the use of immune checkpoint inhibitors for the treatment of malignancies. We present a case of a 77-year-old woman who received anti-PD1 treatment for high-grade invasive urothelial carcinoma, and subsequently presented with weakness, ptosis, and dysarthria concerning for myositis, myocarditis, and myasthenia gravis overlap syndrome. She was successfully treated with high-dose glucocorticoids, mycophenolate mofetil, and intravenous immunoglobulin with resolution of presenting symptoms. To identify cellular subsets that mediated the disease flare, we performed flow cytometry analysis of peripheral blood mononuclear cells collected at baseline, at hospitalization and after treatment with high-dose glucocorticoids. We found an expansion of the memory CD8⁺ T-cell populations at the time of IM3OS presentation. Additionally, we identified a differentiated CD27^- CD28^- effector memory (EM) CD4⁺ subset that was associated with clinical disease activity and contracted with glucocorticoid use administration. This illustrates a unique case of a patient who was successfully treated for IM3OS and highlights the potential use of flow cytometry to provide insight into the underlying pathophysiology of irAEs, and to guide and gauge response to immunomodulatory therapy, thus facilitating a precision medicine approach within the diagnostic and treatment framework for irAEs.