Early onset of ICI-induced myocarditis linked to higher mortality risk

Immune checkpoint inhibitor-induced myocarditis within the first month of treatment initiation appeared linked to a higher risk for death from the condition in patients with cancer, according to retrospective study results presented at the American Association for Cancer Research Annual Meeting. Patients who developed myocarditis within a month of starting immune checkpoint inhibitors appeared 2.6 times more likely to experience a fatal outcome than those with onset in the 1-to-3-month window, and they maintained a twofold higher risk compared with those who developed the condition later in the first year after initiation.

The study used VigiBase, a WHO database that includes more than 40 million reports of suspected adverse drug reactions around the world, to identify cases of immune checkpoint inhibitor-induced myocarditis, myositis and myasthenia gravis among individuals with cancer. Investigators identified 4,635 cases of myocarditis, myositis or myasthenia gravis and classified them into one of seven groups based on whether the conditions occurred alone or in combination.

More than half of cases (57.8%; n = 2,679) included immune checkpoint inhibitor-induced myocarditis, with a majority (71.3%; n = 1,911) being myocarditis alone and the remainder (28.7%; n = 768) co-occurring with myositis and/or myasthenia gravis. Myocarditis with myositis accounted for most of the cases with co-occurring conditions (n = 405), followed by triple M overlap syndrome, or TMOS, (n = 207), and myocarditis with myasthenia gravis (n = 156).

Analyses adjusted for several variables, including cancer type, age and immune checkpoint inhibitor regimen, revealed a significant association between early onset of immune checkpoint inhibitor-induced myocarditis and risk for myocarditis-specific fatality. Risk for myocarditis-specific death also appeared elevated among patients who developed myocarditis with co-occurring myositis and myasthenia gravis.

Immune checkpoint inhibitor-induced myocarditis is rare, with published data suggesting incidence of 0.5% to 1%. Published data cited in the study indicate that anywhere from 20% to 50% of myocarditis cases may be fatal.