MG, heart inflammation develops in man after anticancer therapy
How immune checkpoint inhibitors induce disorder needs to be studied more
The case of a 72-year-old man who developed myasthenia gravis (MG) and myocarditis, or inflammation of the heart, following chemoimmunotherapy for gastric cancer that included sintilimab showcases the need to better understand how this treatment can induce the immune disorder, said researchers in China.
Sintilimab is a type of anticancer therapy that belongs to the class of immune checkpoint inhibitors, that is, medications that help the immune system recognize and attack cancer cells, whose use has been associated with myocarditis and immune-related adverse events.
“The present case report demonstrates the importance of improving the current understanding of [immune checkpoint inhibitors]‑induced myasthenia gravis with concomitant myocarditis following the administration of sintilimab in order to improve clinical outcomes,” the researchers wrote.
The case was detailed in the study, “Myasthenia gravis and myocarditis induced by chemoimmunotherapy in locally advanced gastric cancer: A case report,” in Experimental and Therapeutic Medicine.
In MG, symptoms of muscle weakness and fatigue are generally caused by self-reactive antibodies that target proteins at the neuromuscular junction, the site where nerve and muscle cells communicate to control voluntary movements.
Anticancer treatment leads to MG, heart problems
Here, researchers in China write about a 72-year-old man diagnosed with locally advanced gastric cancer who was treated with a combination of chemotherapy and immunotherapy medications, including oxaliplatin, tigio, and sintilimab.
Nineteen days after his first cycle of therapy, the man developed left eyelid droopiness, double vision, and had difficulty urinating. He had normal muscle strength in all his limbs and had no difficulty breathing, swallowing, or speaking. An electrocardiogram of his heart showed an irregular heartbeat and heart structural issues, and blood work indicated heart muscle damage. The man was diagnosed with immune‑associated myocarditis combined with MG.
The immune checkpoint inhibitors were discontinued and, within 24 hours of being admitted, the patient was started on intravenous, or into-the-vein, methylprednisolone at 80 mg/day along with acid suppression and therapy to protect the heart muscle from damage.
His double vision persisted and eyelid droopiness became more severe, leading to an increase in methylprednisolone to 200 mg/day and to initiating immunoglobulin therapy at 20 g/day.
Five days after he was admitted, the man started having difficulty speaking and had a complete atrioventricular block, which happens when there is an interruption in the transmission of electrical signals from the heart’s upper chambers (atria) to its lower chambers (ventricles). A temporary pacemaker was inserted, given that the man also had heart rate fluctuations.
The biomarkers of heart muscle damage progressively decreased and the pacemaker was removed after an electrocardiogram showed his atrioventricular conduction had improved. However, he started having difficulty swallowing a day later and was started on trozumab, an immunosupressant therapy.
About a month after being admitted, the man’s eyelid droopiness and difficulty swallowing eased, and his speech was more articulated. The methylprednisolone was reduced to 40 mg/day and immunoglobulin therapy to 5 mg/kg, and he was discharged.
Biomarkers of heart damage dropped to normal levels after a month and, after two months, the man started conventional chemotherapy. No recurrence of previous MG symptoms was observed.
“The present case presented is, to the best of our knowledge, the first reported case of a patient with locally advanced gastric cancer who developed immune-related myasthenia gravis and myocarditis, and survived,” the researchers wrote. “There are a number of urgent problems to solve, such as the few management strategies for chemoimmunotherapy-induced myasthenia gravis and myocarditis in locally advanced gastric cancer and the long-term follow-up and care of such patients.”
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