1180 Evaluating predictors of adverse outcomes to immune checkpoint inhibitor-related overlap syndrome of myocarditis, myositis and myasthenia gravis triple M overlap syndrome (TMOS)

<h3>Background</h3> Immune checkpoint inhibitor (ICI) use is associated with a spectrum of immune-related adverse event (irAEs) including myocarditis (MC), myositis (MYS) and myasthenia gravis (MG) - triple M overlap syndrome (TMOS). Individual case reports have highlighted the adverse prognosis of TMOS patients. We sought to evaluate clinical variables to more accurately prognosticate TMOS outcomes. <h3>Methods</h3> Patients with solid tumors who received ≥1 dose of PD-1, CTLA-4, or combination ICI were queried using an institutional ICI registry. Eligible patients carried an ICD10 diagnosis of either MC, MYS or MG, and all patients underwent manual chart review to confirm co-occurrence of all 3 irAEs confirming TMOS. Clinical, biochemical, and disease-specific factors were abstracted to identify predictors associated with TMOS outcome. <h3>Results</h3> Among 21 patients with clinically confirmed MC, 11 patients with TMOS were identified. TMOS patients had a median age of 71.4 years, with females comprising 66.6% of the cohort. Melanoma was the most common indication for ICI use. Compared to non-TMOS MC patients, TMOS patients had a trend towards earlier onset of symptoms. TMOS patients had significantly higher initial (P-value=0.04) and peak (P-value=0.04) creatine kinase levels, along with a trend towards higher mortality rate. <h3>Conclusions</h3> MC in general, and TMOS in particular, are uncommon complications of ICI use. We identified initial and peak creatine kinase levels as potential clinical biomarkers of TMOS development. These findings underscore the association of the 3M overlap syndrome with faster symptom onset and a more severe clinical course, emphasizing the need for early recognition and targeted interventions in these high-risk patients.