Abatacept vs. conventional therapy in immune checkpoint inhibitor-associated myocarditis

Background/Introduction Immune checkpoint inhibitor (ICI)-associated myocarditis is a severe and potentially fatal adverse event with high mortality. Although high-dose corticosteroids are the current standard treatment, evidence supporting additional immunosuppressive therapy in steroid-refractory or fulminant cases is limited. Abatacept, a cytotoxic T-lymphocyte-associated protein-4 immunoglobulin, has been proposed as an effective second-line treatment for ICI-associated myocarditis. Purpose This study aims to evaluate the efficacy of abatacept in the treatment of ICI-associated myocarditis in patients with cancer. Methods We retrospectively analyzed 23 consecutive cases of ICI-associated myocarditis treated with high-dose corticosteroids between March 2017 and February 2025. Clinical outcomes were compared between patients treated with abatacept and those who received conventional therapy without abatacept. Conventional therapy was defined as high-dose corticosteroids (1000 mg/day), with or without intravenous immunoglobulin (IVIg). Results Seven patients received abatacept treatment, while 18 received conventional therapy. There were no significant differences in baseline characteristics between the abatacept and conventional therapy groups, including age (71 [62–75] years vs. 73 [70–75] years, p=0.440), sex (male: 57.1% vs. 75.0%, p=0.626), median time from ICI initiation to myocarditis onset (21 [17–44] days vs. 31 [28–60] days, p=0.228), and combination of ICIs (42.9% vs. 18.8%, p=0.318). The left ventricular ejection fraction on admission was also similar between groups (53.4 ± 23.5% vs. 56.4 ± 14.3%, p=0.947). No significant difference was observed in peak troponin I levels (14,890 [3,633–23,089] pg/ml vs. 1,973 [794–8,537] pg/ml, p=0.114). Fulminant myocarditis was significantly more common in the abatacept group than in the conventional therapy group (6 [85.7%] vs. 2 [12.5%], p=0.002). Similarly, steroid-refractory myocarditis was more frequent in the abatacept group (6 [85.7%] vs. 5 [31.2%], p=0.027). Patients in the abatacept group required more inotropes (4 [57.1%] vs. 2 [12.5%], p=0.045) and IVIg (5 [71.4%] vs. 3 [18.8%], p=0.026) than those in the conventional therapy group. They also tended to require more intensive care interventions, such as intubation and/or mechanical circulatory support. However, there was no significant difference in cardiac mortality between the abatacept and conventional therapy groups (1 [14.3%] vs. 2 [12.5%], p=1.000) (Table). Conclusion(s) Abatacept may represent a promising second-line treatment for ICI-associated myocarditis, particularly in severe cases such as fulminant or steroid-refractory myocarditis. Further research is required to validate these findings and establish optimal management strategies for this life-threatening condition.