Case Presentation: Case1: A 72- year old male with a diagnosis of stage four non-small cell Lung carcinoma who was treated with Pembrolizumab, presented two weeks after his first dose with generalized body aches and weakness. Labs showed elevated creatinine Kinase, increased serum creatinine with hyperkalemia to 5.6 and elevated troponins to as high as 116u/l. Hospital Course was later complicated with sinuses pauses and persistent bradycardia. Review of systems was positive for mild shortness of breath and negative for chest pain. EKG was suggestive of peaked T waves initially, which progressed to a ventricular rhythm with a wide QRS complex. After exclusion of other possible etiologies, a diagnosis of Myocarditis secondary to Pembrolizumab was made. Despite aggressive treatment with transvenous pacing, high dose corticosteroids and hemodialysis patient rapidly worsened and expired from a cardiac arrest.
Case2: A 77- year old male with stage 4 urothelial cancer treated with Pembrolizumab presented 2 weeks after his second dose with dysphagia, dyspnea and failure to thrive. On examination, he was found to have diplopia, ptosis and respiratory distress. Lab work was positive for acetylcholine modulating receptor antibodies and anti-smooth muscle antibodies. Given the absence of symptoms prior to initiation of Pembrolizumab, the diagnosis of Immune-related Myasthenia Gravis was made over Paraneoplastic Myasthenia. The patient was initially treated with Prednisone and IVIG with the slight improvement, but eventually required therapeutic plasma exchanges with significant improvement of his symptoms.

Discussion: Pembrolizumab, a monoclonal antibody which inhibits programmed cell death 1 receptor has been shown to enhance immunity against malignant cells. Immune checkpoint inhibitors have revolutionized the management of a wide variety of malignancies including NSCLC, Hodgkin’s lymphoma, melanoma, urothelial, head and neck, and microsatellite instability cancers. The common side effects include endocrine abnormalities, fatigue, anemia, and decreased appetite. However, safety concerns must also be taken into consideration, as Pembrolizumab has been associated with several immune-related adverse events (irAEs).

Conclusions: Although this medication is well tolerated, several immune-related adverse events have been documented. To our knowledge, so far 9 cases of Pembrolizumab induced new onset Myasthenia gravis and 4 cases of Myocarditis were reported in the literature. Myocarditis has the highest fatality rates (52%), whereas endocrine events and colitis had the least fatalities of all the irAEs. Steroids remained the mainstay of the treatment, with IVIG and plasmapheresis for severe cases. Healthcare professionals, especially hospitalists need a high level of suspicion for irAEs as early detection might limit morbidity and mortality.