Durvalumab-induced Myocarditis, Myositis, and Myasthenia Gravis

A Case Report

Jason Cham; Daniel Ng; Laura Nicholson


J Med Case Reports. 2021;15(278) 

In This Article

Case Presentation

A 72-year-old Caucasian man with a history of prostate cancer, central serous retinopathy, obstructive sleep apnea, type 2 diabetes mellitus, hypertension, and mild chronic obstructive pulmonary disease but no known coronary artery disease or history of neurologic disorders was first diagnosed with left lower lobe non-small cell lung cancer (NSCLC) in 2013, for which he underwent a left lower lobectomy that same year. On surveillance imaging in 2014, he was noted to have a right lower lobe nodule and was diagnosed with a second primary NSCLC, for which he underwent stereotactic body radiation therapy (SBRT). In 2017, he was noted to have an enlarging left upper lobe nodule that was treated with SBRT. Surveillance CT imaging in September 2018 was significant for an enlarging right upper lobe nodule with right paratracheal lymph node involvement. Subsequent positron emission tomography (PET)-CT revealed several FDG-avid mediastinal and right hilar nodes concerning for malignancy. Metastatic bronchogenic adenocarcinoma was confirmed via endobronchial ultrasound with transbronchial needle aspiration, with pathology showing 5/5 positive lymph nodes. PD-L1 immunohistochemistry 22C3 (Keytruda) testing of the lymph node revealed high PD-L1 expression with 80% tumor proportion score. MRI of the brain was negative for intracranial metastatic disease. He was diagnosed with TxN3M0 stage IIIB adenocarcinoma and was treated with six cycles of weekly cisplatin and SBRT. He then initiated adjuvant durvalumab for maintenance therapy, receiving two cycles (10 mg/kg) on treatment days 0 and 15. Our patient subsequently presented to the emergency department on day 18 with a 4-day history of shortness of breath, weakness, and chest pressure. Workup on admission was significant for lateral lead ST elevations with an initial troponin of 7.1 ng/dL. He emergently underwent a left heart catheterization, which was negative for obstructive coronary artery disease. Transthoracic echocardiogram was significant for a normal ejection fraction with mild left ventricular concentric hypertrophy.

Admission diagnosis was myopericarditis of unclear etiology. On hospital day 4, he was noted to have persistently elevated levels of serum troponin, peaking at 12 ng/mL. His levels of serum creatinine kinase (CK) were elevated as well, peaking at 9262 U/L. He had persistent mild hepatocellular transaminitis (peak AST 72, ALT 531). The use of corticosteroids was discussed with the patient owing to concern for irAE; however the patient declined on the basis of his central serous retinopathy. He was noted to have dysphagia on admission with regurgitation of solids and liquids. A barium swallow study and esophagogastroduodenoscopy on hospital day 3 did not reveal any structural abnormalities. On hospital day 9, the patient developed progressive axial weakness, with increasing difficulty holding his head upright while seated. Neurology was consulted, who had a high concern for myasthenic crisis, which was subsequently confirmed by decreased negative inspiratory forces and elevated acetylcholine receptor binding and blocking antibodies. Due to his declining respiratory status, he was transferred to the intensive care unit (ICU) and intubated on the same day for airway protection. MRI of the brain performed on hospital day 10 was significant for 12 new metastatic lesions with surrounding vasogenic edema. The patient was started on high-dose corticosteroids at 1 mg/kg/day and underwent plasmapheresis on hospital day 10, completing 5 rounds. Unfortunately, he was unable to be weaned from mechanical ventilation and required tracheostomy placement as well as percutaneous endoscopic gastrostomy nutrition.

After multiple goals-of-care discussions, the patient was transferred from the ICU to a long-term acute care facility owing to mechanical ventilation dependence, on hospital day 36. Diagnoses of myopericarditis, myositis, and myasthenic crisis were attributed to immune-mediated response to durvalumab.