TY - JOUR
T1 - Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis
T2 - Pathway toward precision-based therapy
AU - Balanescu, Dinu Valentin
AU - Donisan, Teodora
AU - Palaskas, Nicolas
AU - Lopez-Mattei, Juan
AU - Kim, Peter Y.
AU - Buja, Louis Maximilian
AU - McNamara, Dennis M.
AU - Kobashigawa, Jon A.
AU - Durand, Jean Bernard
AU - Iliescu, Cezar A.
N1 - Funding Information:
The University of Texas MD Anderson Cancer Center is supported in part by the National Institutes of Health through Cancer Center Support Grant P30CA016672 .
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.
AB - Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.
KW - Cardio-oncology
KW - Immune checkpoint inhibitors
KW - Immune-related adverse events
KW - Immunotherapy
KW - Myocarditis
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U2 - 10.1016/j.carpath.2020.107211
DO - 10.1016/j.carpath.2020.107211
M3 - Article
C2 - 32268262
AN - SCOPUS:85082737447
SN - 1054-8807
VL - 47
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
M1 - 107211
ER -