Successful rescue therapy with eculizumab for probable tislelizumab-related MMM overlap syndrome with dual positivity for anti-acetylcholine receptor and anti-titin antibodies: a case report and literature review.

Abstract / Summary

While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, they can trigger diverse immune-related adverse events (irAEs). Among these, ICI-related myocarditis, myositis and myasthenia gravis (MMM) overlap syndrome (ICI-MMM) is a rare but potentially fatal complication. Conventional immunotherapy often exhibits limited efficacy against ICI-MMM, which is associated with high mortality rates. Thus, there is an urgent need for novel and effective strategies to mitigate its life-threatening outcomes. We conducted a retrospective analysis of the successful rescue use of eculizumab in a patient with tislelizumab-related MMM overlap syndrome who tested seropositive for both anti-acetylcholine receptor (AChR) and anti-titin antibodies. We also performed a focused systematic literature review on the use of complement inhibitor therapy for ICI-related myasthenia gravis and its overlap syndrome. A 64-year-old male developed ptosis and tetraparesis two weeks following the second infusion of tislelizumab for lung adenocarcinoma. Serological testing revealed dual positivity for anti-AChR antibody and anti-titin antibody. Tislelizumab was immediately withdrawn, and the patient was treated with corticosteroids and intravenous immunoglobulin as first-line therapy. However, his clinical condition deteriorated rapidly, and new symptoms emerged, including chest pain, muscle pain, dysphagia, slurred speech, and dyspnea. Although the absence of histopathological confirmation for myocarditis and myositis, the clinical, laboratory, electrophysiological, and cardiac imaging findings supported the diagnosis of probable ICI-MMM. Rescue therapy with eculizumab was commenced (900 mg weekly for four doses), eliciting rapid and marked clinical improvement. The patient ultimately achieved minimal symptom expression without any exacerbation. This is the first reported case of successful eculizumab rescue treatment for probable tislelizumab-related MMM overlap syndrome with dual seropositivity. Our finding suggests eculizumab may represent a promising rescue option for ICI-MMM warranting prospective evaluation.

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