Stage 4 lung cancer: managing pembrolizumab-induced myasthenia gravis

What happened, in summary

A 71-year-old woman had Stage IV lung adenocarcinoma diagnosed 3 years before she came to the emergency department with gradually worsening shortness of breath and orthopnea. Her cancer had first been treated with 6 cycles of systemic chemotherapy. After a partial response, she underwent right upper lobe posterior segmentectomy 8 months after diagnosis. Seventeen months later, the disease progressed, and she received 6 cycles of carboplatin, pemetrexed, and pembrolizumab every 3 weeks. She achieved a complete response and continued maintenance pemetrexed plus pembrolizumab, completing 3 maintenance cycles before this presentation. Her new breathing problems were initially evaluated for infection, pulmonary embolism, cancer recurrence, and other lung causes. Bronchoscopy did not show tumor, infection, or malignant cells. Pulmonary function testing, diaphragm ultrasound, and respiratory muscle measurements raised concern for neuromuscular weakness. Blood testing then showed elevated anti-acetylcholine receptor antibody, confirming myasthenia gravis attributed to pembrolizumab-related immune dysregulation. She also had marked thyroid-stimulating hormone elevation, consistent with another immune-related endocrine effect. Pembrolizumab-based treatment was stopped, and she received nocturnal non-invasive ventilation, prednisolone 75 mg daily, pyridostigmine 120 mg daily, levothyroxine 88 µg daily, and IVIG for 5 days, with additional IVIG courses planned. At 2 months, breathing tests and imaging had improved. At 9 months, her lung cancer remained in complete response while she continued low-dose prednisolone, pyridostigmine, levothyroxine, and nighttime ventilatory support. Her workup also showed type 1 respiratory failure at presentation, severe mixed ventilatory impairment, reduced diaphragm excursion, and a marked drop in supine forced vital capacity, helping explain why neuromuscular weakness became central to her care.