Treatment for thymoma with the immune checkpoint inhibitor (ICI), sintilimab, resulted in immune-related adverse events (irAEs), including secondary myasthenia gravis (MG) and lethal myocarditis, according to a case report published in the journal Medicine.
The 45-year-old female patient was initially diagnosed with metastatic thymoma type B2 and was treated with 1 cycle of chemotherapy with nab-paclitaxel and carboplatin combined with sintilimab. After 14 days, she was admitted to the hospital with abdominal pain, dizziness, and intermittent chest tightness. Two days after admission, the patient also began reporting fatigue and ptosis.
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Electromyogram of bilateral facial nerves showed attenuation in the amplitude of wave 5 following low-frequency electrical stimulation, the researchers found. Testing also revealed positive results for antiacetylcholine receptors antibodies. These 2 results indicated secondary MG, they added.
Lab testing also revealed elevated myocardial enzyme indicators, but ECG and ultrasound revealed no signs of acute coronary syndrome and no systolic dysfunction of the left ventricle. Coronary artery computed tomography angiography did not reveal any pathogenic stenosis.
Pulmonary embolism, myocardial infarction, and aortic dissection were ruled out with further testing. Uremic cardiomyopathy, heart failure, cardiomyopathy, and viral myocarditis were also ruled out following other testing results. The combination of the patient’s medical history, symptom onset time, and negative results of the differential diagnosis of other cardiac issues led to the diagnosis of ICI-induced myocarditis and MG.
“The [ICI] therapy in thymoma [shows] promising results, but the life-threatening irAEs [are] the biggest risk. A major challenge to consider while treating thymoma patients is how to screen the immunotherapy benefit groups or exclude high-risk groups of adverse events, and how to make immunotherapy a safe and effective option,” the authors wrote.
Sintilimab is a fully recombinant human antiprogrammed cell death-1 (PD-1) immunoglobulin G 4 monoclonal antibody. It can bind to PD-1 to inhibit the binding of PD-1 receptors on T cells to the PD-1 ligands on tumor cells. This action can activate cytotoxic T lymphocytes and lead to improved antitumor activity.
Wang C, Zhong B, He J, Liao X. Immune checkpoint inhibitor sintilimab-induced lethal myocarditis overlapping with myasthenia gravis in thymoma patient: a case report. Medicine. Published online April 14, 2023. doi:10.1097/MD.0000000000033550