Does early recognition and treatment of immune-related myositis and myasthenia gravis reduce mortality of immune-related myocarditis?

Abstract

12025 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, some immune-related adverse events (irAEs) can be severe, even fatal. ICI-induced myocarditis (ICI-M) carries the highest mortality rate of 30-50%. Notably, ICI myocarditis frequently co-occurs with ICI-induced myositis (ICI-M 2 ) or as a triad of ICI-induced myocarditis, myositis and myasthenia gravis (ICI-M 3 ). Despite this known association, it remains unclear whether these entities represent distinct disease processes or a spectrum of disease severity. Therefore, we sought to compare outcomes among those diagnosed with ICI-M, ICI-M 2 and ICI-M 3 . Methods: We performed a single-institution retrospective cohort study using the electronic health record to identify patients seen in a solid tumor clinic between 1/21/11 – 1/21/25, who had received ICI therapy. There was a concern for myocarditis in 82 patients, of which 33 were deemed to have > grade 2 ICI-induced myocarditis. Of the 33 cases, 36% had ICI-M, 36% had ICI-M 2 and 27% had ICI-M 3 . We then assessed differences in age, sex, cancer type & stage, immunotherapy regimen, number of immune suppressants given, myocarditis grade, and overall survival across these groups. Results: The Table shows patients with ICI-M presented at an earlier cancer stage and more commonly after ICI monotherapy than combination therapy. Despite this, these patients typically had more severe grade ≥ 3 myocarditis (75%) compared with ICI-M 2 (42%) and ICI-M 3 (44%) and had a worse overall survival (33%) as compared to ICI-M 2 and ICI-M 3 (67% and 78% respectively). Notably ICI-M patients typically presented with cardiac-specific symptoms and presented after more cycles of ICI therapy (avg. of 4 cycles). In contrast, ICI-M 2 and ICI-M 3 patients presented after fewer ICI cycles (avg. of 2 cycles) with symptoms of myositis or myasthenia. They typically did not present with cardiac-specific symptoms and were then incidentally found to have mildly elevated troponin levels. Conclusions: Patients with ICI-M presented after more ICI cycles, had more severe myocarditis and worse overall survival as compared to ICI-M 2 and ICI-M 3 patients. Our findings suggest that patients who developed concurrent symptoms of myositis or myasthenia gravis, prompted earlier recognition of mild myocarditis, leading to earlier initiation of immunosuppressive treatment thereby improving clinical outcomes. ICI-M (n = 12) ICI-M 2 (n = 12) ICI-M 3 (n = 9) Total (n = 33) Median Age (yrs) 67 64 77 69 Sex (% male) 50 83 56 64 Cancer type (% melanoma) 42 75 44 55 Cancer stage (% stage IV) 67 92 78 82 ICI treatment (% dual ICI) 33 67 56 55 Avg. # of cycles before toxicity (range) 4.2 (1-13) 2.2 (1-4) 2.1 (1-3) 2.8 (1-13) Severity of myocarditis (% grade ≥ 3) 75 42 44 55 Immunosuppressant agents (% given 2 or more agents) 50 33 78 52 Overall survival (% alive) 33 67 78 58