Case Presentation: A 78-year-old gentleman with a past medical history of scalp melanoma, renal papillary cell carcinoma, Ewing sarcoma, and end-stage renal disease presented to an outpatient Oncology appointment with bilateral ptosis, diplopia, myalgias, and bilateral proximal leg weakness less than one week following pembrolizumab infusion and influenza vaccination. He was sent to outpatient Neurology due to concern for immune checkpoint inhibitor (ICI)-induced myositis. Differential diagnosis included ICI-induced myositis and myasthenia gravis, with less likelihood for bilateral neuropathy with polyradiculopathy. EMG was performed and was consistent with a diffuse myopathic process affecting the cranial muscles as well. Creatine kinase was elevated at 3224 and troponin was elevated at 1237. A number of additional tests were obtained that all came back negative, including myasthenia gravis evaluation with MuSK reflex, MyoMarker 3, pernicious anemia cascade, necrotizing myopathy panel, and paraneoplastic panel. MRI brain was negative for evidence of residual/recurrent or metastatic disease. PET scan showed multifocal intramuscular FDG activity suggestive of possible myositis. Due to new concern for ICI-induced myocarditis, in addition to myositis, the patient was admitted to the hospital for cardiac monitoring and was started on a 5-day course of 1 g IV methylprednisolone sodium succinate. Transthoracic echocardiogram was unremarkable, but cardiac MRI with gadolinium demonstrated findings compatible with acute myocarditis. While on high-dose IV steroids, the patient also received PCP prophylaxis with sulfamethoxazole-trimethoprim, GI prophylaxis with pantoprazole, and calcium and vitamin D supplementation. Creatine kinase and troponin continued to downtrend during the hospitalization and the patient was discharged on 2 mg/kg/day of prednisone with follow up scheduled in the ICI Toxicity Clinic 48 hours later.
Discussion: Despite their important role in the clinical management of several neoplasms, immune checkpoint inhibitors – such as PD-1, PD-L1, and CTLA-4 inhibitors – have rare but serious side effects that warrant immediate recognition and close management. Labs and imaging should be obtained immediately while preparing treatment for patients who present with sudden symptoms following ICI infusion. Unfortunately, there are no prospective trials that outline treatment of immune-related adverse events (irAEs), so treatment is based on clinical experience. In the event of suspicion for an irAE, the ICI should be stopped immediately and glucocorticoids started simultaneously to optimize outcomes. Per the American Society of Clinical Oncology’s guidelines, 1-2 mg/kg/day of prednisone should be initiated for ICI-induced myositis and/or myocarditis and then slowly tapered as creatine kinase and/or troponin levels decrease. However, the early institution of cardiac transplant rejection doses of steroids (1 g/day) should be considered given the aggressive nature of ICI-induced myocarditis. Patients need to be closely followed after hospitalization to ensure improvement of toxicity.
Conclusions: Hospitalists should be familiar with ICI-induced toxicities as the use of these novel monoclonal antibodies has been widely increasing. Special consideration should be given to patients receiving these medications as the prompt recognition and management of their toxicities can alleviate devastating complications.
