Novel use of abatacept and ruxolitinib as salvage therapy in steroid-refractory immune checkpoint blockade-induced myocarditis with myasthenia and myositis overlap syndrome

An 81-year-old female with stage IIIB melanoma presented to an outside hospital complaining of fatigue, muscle aches, shortness of breath, eyelid drooping, and difficulty swallowing. Two weeks prior, she had received her first and only dose of PD-1 blockade, nivolumab. A 12-lead electrocardiogram at the time of admission revealed sinus tachycardia at 106 beats per minute. Lab investigations were remarkable for elevated high-sensitivity troponin-T levels of 762 ng/mL (reference range < 11 ng/mL). Creatinine kinase (CK) levels were elevated at 4033 IU/L (reference range: 34-145 IU/L) and acetylcholine receptor binding antibody was positive at 0.28 nmol/L (reference range <0.02 nmol/L). A 2-D transthoracic echocardiogram demonstrated normal ejection fraction without wall motion abnormalities. With evidence of cardiac damage, along with eyelid and bulbar weakness, in the context of recent administration of an immune checkpoint blocker (ICB), this constellation of symptoms raised suspicion for the immune-related adverse event (iRAE) described as ICB-induced myocarditis with myasthenia and myositis overlap syndrome (IM3OS). The patient received a five-day course of daily methylprednisolone 1 mg/kg IV and 1 g/kg IVIG, along with daily 60 mg pyridostigmine IV. Over the following eight days, her presenting symptoms improved, cardiac troponin down trended (960 ng/mL), and she was discharged to a rehabilitation facility with daily 60 mg prednisone PO.