(180) Tremelimumab/Durvalumab-Induced Myocarditis and Complete Heart Block

Introduction: Immune checkpoint inhibitors (ICI) like tremelimumab and durvalumab are associated with colitis, pneumonitis, hepatitis, and myocarditis (1). Although rare (incidence of 0.04-1.14%), myocarditis has the highest documented fatality rate (1,4). Major cardiovascular events are reported in association with myocarditis including cardiogenic shock, arrest, and complete heart block (CHB). CHB is noted in 8% of patients with documented myocarditis and is a major predictor of mortality (2,5). This case discusses myocarditis complicated by CHB after ICI therapy initiation.

Description: A 60-year-old male with metastatic adenoid cystic carcinoma treated with tremelimumab/durvalumab presented to the hospital 20-days after his first infusion with fatigue and shortness of breath. On presentation, troponin was elevated but electrocardiogram (EKG) was without ST changes. Subsequently, 2 days after admission, suffered cardiac arrest which required placement of an intraaortic balloon pump and pacemaker given hemodynamic instability and refractory bradycardia. Left heart catheterization was without coronary artery disease. Ultimately, it is thought that tremelimumab/durvalumab therapy lead to myocarditis with complete heart block. The patient was started on high dose methylprednisolone with plans to start inpatient Infliximab. Unfortunately, he developed multiorgan failure and elected to pursue comfort measures.

Discussion: ICIs are known to have a vast side effect profile. In this case, myocarditis developed rapidly after combination therapy, a notably rare complication typically seen 17-34 days post-treatment (3). Specifically with ICI induced myocarditis, there is a 35-50% mortality rate. However when myocarditis mortality rates were separated between combination and monotherapy, rates were 67% and 36% respectively (3). This is interesting given that combination therapy is more effective however carries greater myocarditis mortality risk. Interestingly, in many cases of myocarditis secondary to ICI, individuals had normal left ventricle ejection fraction and EKG pre-ICI, which warrants discussion of further screening for individuals at risk of developing this rare adverse effect (5). Overall, this is a rare case of ICI combination therapy induced myocarditis that progressed to CHB and cardiac arrest.