Immune checkpoint inhibitor-induced myocarditis in cancer patients: a case report and review of reported cases

Background: Immune checkpoint inhibitor (ICI) induced myocarditis is a rare, severe, and often fatal adverse event. Evidence to guide appropriate immunosuppressive therapy is scarce. We present a case of ICI-induced myocarditis and a review of ICI-induced myocarditis cases to determine the most effective immunosuppressive therapeutic strategy for ICI-induced myocarditis.

Methods: A systematic search of PubMed was carried out for treatment of ICI-induced myocarditis. Reference lists from identified articles were manually reviewed for additional cases.

Results: A total of 87 cases with ICI-induced myocarditis were identified. The majority were melanoma (n = 39), lung cancer (n = 19), renal cell cancer (n = 10), and thymoma cancer patients (n = 4). In 38 (44%) cases, patients received high-dose steroid treatment only. A total of 49 (56%) cases were treated with immunosuppressive agents other than steroid; a total of 13 different immunosuppressive agents were used, including alemtuzumab or abatacept. The median time to onset of symptoms after initiation of ICI was 16 days (range, 1-196 days); cardiotoxic symptoms developed after 2 cycles of ICI (range, 1-13 cycles). A total of 48% of cases were fatal. In cases treated with high-dose steroids only vs. cases treated with other immunosuppressive agents, fatality was 55% and 43% respectively. In 64 out of the 87 cases, tumor control was not described. In patients treated with high-dose steroids only, two patients had stable disease as best tumor response; in patients treated with other immunosuppressive agents, one complete response, one partial response and seven stable disease were noted as best tumor response. Overall, 11 studies were at low risk of bias (12.6%), 38 at moderate risk of bias (43.7%) and 38 at high risk of bias (43.7%).

Conclusion: Immune checkpoint inhibitor induced myocarditis is a serious and often fatal adverse event. High-dose prednisolone, alemtuzumab or abatacept are all possible treatments options for ICI-induced myocarditis, whereas infliximab increases the risk of death from cardiovascular causes, and should be avoided. Further research is needed.