Amiodarone/pembrolizumab

Abstract

Myocarditis, myasthenia gravis and lack of efficacy: case report A 78-year-old woman developed myocarditis and myasthenia gravis during treatment with pembrolizumab. Additionally, she exhibited lack of efficacy during treatment with amiodarone for ventricular tachycardia. The woman with history of hypertension, type 2 diabetes mellitus and hyperlipidaemia had been diagnosed with stage 3C, BRAF wild-type left knee melanoma. Subsequently, she underwent local excision and sentinel lymph node surgery. Then she started receiving adjuvant pembrolizumab 2 mg/kg every 3 weeks [route not stated]. After 2 weeks of the second pembrolizumab dose, she presented to the emergency department with a 5 day history of exertional dyspnoea and dysphagia. Ensuing cardiovascular examination revealed an irregular heart rate and signs of heart failure (HF). Neurological examination showed bilateral asymmetric ptosis with fatigability and proximal muscle weakness. Blood test showed elevated high-sensitivity troponin-T, N-terminal pro-Btype natriuretic peptide and creatine kinase. ECG showed atrial tachycardia with new right bundle branch and left anterior fascicular block, while, transthoracic echocardiogram revealed a left ventricular ejection fraction (LVEF) of 65% with hypokinesis of the basalto-mid-inferior wall and basal inferoseptum. Subsequent cardiovascular magnetic resonance (CMR) imaging was nondiagnostic as she was noncompliant. Coronary angiography showed no flow-limiting disease. Single-fiber electromyography of the frontalis muscle revealed abnormalities compatible with myasthenia gravis (MG); acetylcholine receptor antibody (AchR-Ab) was negative. She was diagnosed with immune-related adverse events related to immune checkpoint inhibitor (ICI) i.e. pembrolizumab including myocarditis and neuromuscular complications [duration of treatment to reaction onset not stated]. The woman therefore started receiving treatment with methylprednisolone. On day 2 of admission, she developed monomorphic ventricular tachycardia and received IV amiodarone [dosage not stated]. Later on the same day, she developed high-grade atrioventricular block and R-on-T polymorphic ventricular tachycardia. Therefore, resuscitation with four shocks and a temporary pacemaker was applied. Subsequently, her condition stabilised with methylprednisolone; however, switching to oral prednisone resulted in a recurrent increase in troponin. Therefore, mycophenolate-mofetil was added. Due to persistent troponin elevation secondary to malignant presentation, she was started on abatacept. After the first dose of abatacept, she was transferred to other facility. At that time, a repeat CMR demonstrated features of myocarditis. She also started receiving treatment with spironolactone and furosemide for HF with preserved LVEF (56% by CMR) and bisoprolol for paroxysmal atrial tachycardia. After two doses of abatacept, her HF symptoms significantly improved. Therefore, supplemental oxygen was discontinued, and she was transitioned to oral diuretics. During abatacept treatment, her B-type natriuretic peptide peaked at 623 pg/mL, which decreased to 269 pg/mL immediately post-treatment. She received plasmapheresis for persistent neurological symptoms with good response. Following abatacept therapy and plasmapheresis, her high-sensitivity troponin-I (hsTnI) level stabilised and gradually decreased on a slow prednisone taper. No recurrence of heart block or ventricular arrhythmias was noted. After 4 months of stay, she was discharged home. Her discharge hsTnI remained elevated. The prednisone was gradually tapered and discontinued at 5.5 months after index admission, and mycphenolate-mofetil was stopped after a month. After further 2 weeks, her functional status improved; however, hsTnI remained elevated. Further investigation was performed for persistent troponin elevation. The macrotroponin examination result was suggestive of possible partial contribution of macrotroponin (immunoglobulin G [IgG]-troponin complex) to the elevated hsTnI measurements. Repeat CMR showed stable late gadolinium enhancement (LGE), with no myocardial oedema. However, mild worsening biventricular function (LVEF from 56% to 50% and right ventricular ejection fraction from 61% to 46%), along with increased myocardial native T1 levels without elevated T2 levels were suggestive of myocardial fibrosis. She continued to receive cardiac medications along with slow tapering of furosemide. Surveillance CT scans of her melanoma showed no disease recurrence.