Herein, we report a rare case of an elderly patient with durvalumab-associated hidden myocarditis.
The exact mechanism underlying ICI-induced myocarditis remains poorly understood. Although the incidence of cardiac irAE is relatively low, ranging from 0.27–1.14%4,5,6), its fatality rate (50%) is high7). However, we were able to confirm that corticosteroids and IVIG are effective treatments for durvalumab-induced myocarditis.
However, to the best of our knowledge, evidence of the efficacy of both steroid therapy and IVIG in the treatment of irAE-associated myocarditis is still scarce. Nevertheless, there are reports of the efficacy of IVIGs in the treatment of myocarditis with low cardiac function8), and considering the suppressive effects of T cells on IVIG inflammation9), it may be effective in irAE-associated myocarditis.
Elderly patients sometimes have no symptoms or complaints of dyspnea, which may be clinically atypical for each individual. Even in asymptomatic patients, regular echocardiography tests and ECGs can help to detect the disease at an early stage.
casein this case, the condition occurred five months after the administration of an immune checkpoint inhibitor. Although the time between the administration of immune checkpoint inhibitors (ICIs) and the onset of myocarditis is generally considered to be within three months6,7), there are only a few reports on the onset of myocarditis more than one year after the first administration of ICIs to the best of our knowledge.10,11)
Myocarditis is an inflammatory disease of the myocardium caused by cancer, viral infection, autoimmunity, drugs, and eosinophil count elevations.12) Myocarditis is classified as eosinophilic, lymphocytic, giant cell, granulomatous, or pleomorphic based on the type of cells infiltrating the myocardium. ICI-induced myocarditis occurs when ICIs maintain T lymphocyte activity, T lymphocytes infiltrate the myocardium, and the immune response is excessive. Histological analyses of endomyocardial biopsy specimens have revealed myocardial infiltration by CD8-positive lymphocytes and CD68-positive macrophages.13) The histopathological findings in this case were typical of irAE myocarditis (Fig. 3).
Several biomarkers, such as troponin, electrocardiography, and CK, have been shown to be useful for cardiac irAE.14,15)
In the present study, hs-cTn and CK-MB levels were also elevated, and they decreased as the patient’s myocarditis improved. However, NT-proBNP did not change significantly, suggesting that NT-proBNP is not a suitable biomarker for cardiac irAE follow-up.
The recommended regimen after CCRT is one year of durvalumab maintenance therapy. However, in this case, the patient was treated with durvalumab for only six months; notwithstanding, her lung cancer has not worsened for more than two years.
According to several tissue sample analyses, lung cancer patients who experience strong side effects of ICI may also be responsive to ICIs.16,17) In addition, the patient had a TPS of < 1%; however, the ICI administered was effective because it was an immunostain and not a quantitative test; so, errors in the biopsy pathology specimen analysis may have been a factor.
Although there is still insufficient evidence of durvalumab-induced cardiotoxicity, its onset is thought to be dose-independent. Although studies are underway to determine the risk of onset, it is impossible to completely predict the outcome. 18,19) As demonstrated in the present case, the possibility of avoiding death is increased by performing echocardiography regularly to ensure the early diagnosis of myocarditis.
In patients on ICIs, especially elderly patients, it is important to pay attention to irAEs and perform periodic electrocardiograms and ECGs, even in asymptomatic persons, for early detection and prognosis improvement. Considering the paucity of clinical evidence of myocarditis related to PD-L1 treatment, we believe the present case report is of clinical value for the treatment and prognosis of PD-L1-relatedmyocarditis.