Abstract 14926: Case of Severe Myocarditis Associated With Nivolumab-Relatlimab

Introduction: Immune checkpoint inhibitors (ICIs) are the standard of care for cancer but can cause immune-related adverse events (irAEs). Nivolumab/Relatlimab combination was approved in March 2022 for unresectable or metastatic melanoma. Cardiac toxicity associated with ICIs is rare but can be fatal. Prompt recognition is key.

Description: We present a case of an 84-year-old with no cardiac history who experienced worsening fatigue a week after Nivolumab/Relatlimab infusion. This was followed by myalgia, double vision, shortness of breath, and chest heaviness. Her symptoms worsened, and she sought medical care. Tests showed elevated high-sensitivity troponin T and total creatine kinase levels of 1100 and 6000, respectively. Her first EKG revealed first degree AV block. Within hours, she developed a complete AV block. Her initial LVEF was 75%. She was diagnosed with “triple M" syndrome (myositis, myocarditis, and myasthenia) and received pulse-dose steroids and IV immunoglobulin. She developed myasthenic crisis with respiratory failure requiring intubation. Repeat echocardiogram revealed a drop in LVEF to 43% with new regional wall motion abnormalities attributed to worsening myocarditis. Considering fast progression and poor prognosis, the patient and her family chose comfort measures over escalation of care.

Discussion: Myocarditis is a known but rare irAE with reported incidence of less than 1%. It can be associated with myositis and/or myasthenia. Clinical presentation varies, but rapidly progressive conduction disease is one of the most commonly described conditions. Direct T-cell cytotoxicity is the proposed mechanism. Cardiac irAEs can fully resolve if treated early. However, mortality remains elevated.

Conclusion: This is one of the few reported cases of severe myocarditis from Nivolumab/Relatlimab. As the combination is still in phase IV development, more cases may emerge in the future and early recognition is vital.