Background: Immune checkpoint inhibitor (ICI)-related myocarditis is a rare, but potentially life-threatening immune-related adverse event (irAE). When it is accompanied by myositis and myasthenia gravis, the so-called “triple M syndrome,” it represents a complex diagnostic and therapeutic challenge. While high-dose corticosteroids remain first-line treatment for ICI-related myocarditis, a subset of patients, especially those with concomitant myositis and myasthenia gravis, develops steroid-refractory disease requiring early escalation to intensified immunosuppressive therapy.
Case summary: We report a case of a 75 year old male patient with metastatic non-small cell lung cancer (UICC stage IVB) who underwent treatment with carboplatin, pemetrexed and pemprolizumab. Approximately four weeks after initiation of combination therapy, the patient developed elevated cardiac biomarkers, progressive myalgia as well as ptosis and diplopia. Echocardiography demonstrated preserved systolic function. MRI findings were consistent with inflammatory myositis. Further testing confirmed ICI related myocarditis, myositis and myasthenia gravis. The patient was started on high-dose methylprednisolone (1000 mg/day for 5 days) which resulted in a transient improvement. However, relapse occurred during steroid tapering with further elevation of high-sensitivity troponin T, NT-proBNP and CK levels. Consequently, abatacept and mycophenolate mofetil were initiated as adjunct immunosuppressive agents. Following this combination therapy, the patient's clinical condition improved, cardiac biomarkers decreased and muscular symptoms resolved. The patient was discharged home with close multidisciplinary follow-up in our outpatient clinic.
Discussion: This case illustrates the triad of ICI-induced myocarditis, myositis, and myasthenia gravis. The combination of abatacept and mycophenolate mofetil achieved clinical and biochemical stabilization, underscoring their potential role in managing steroid-resistant irAEs. Given the expanding use of ICIs across malignancies, high clinical vigilance, early recognition and multidisciplinary management are essential.
