Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome

Abstract

Although animal studies have shown that the immunomodulator ipilimumab causes inflammation of the myocardium, clinically significant myocarditis has been observed only infrequently. We report a case of suspected acute coronary syndrome without a culprit lesion on cardiac angiography and takotsubo cardiomyopathy (TC)-like appearance on echocardiography in a patient with metastatic melanoma who received four standard doses of ipilimumab. Apical ballooning, hyperdynamic basal wall motion, systolic anterior motion of the mitral valve, and associated severe left ventricular outflow tract obstruction were present. Restaging with positron emission tomography-computed tomography done soon after discharge incidentally revealed increased fludeoxyglucose uptake in the apex. This case illustrates that a TC-like syndrome might be caused by autoimmune myocarditis after ipilimumab treatment although this was not biopsy-confirmed. Post-marketing surveillance should capture cardiac events occurring in patients treated with ipilimumab to better document and clarify a relationship to the drug, and biopsies should be considered. Physicians utilizing this novel agent should be aware of the potential for immune-related adverse events.

Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action

“…The first specific report of myocarditis during treatment with a PD‐1/PD‐L1 inhibitor was published in 2014 [27], and a number of cases of ICI‐associated myocarditis have been described since . In an early analysis of more than 20,000 patients treated with ICIs, either alone or in combination, the incidence of myocarditis was 0.09%; the incidence of fatal myocarditis in this sample was 0.03% .…”

Management of side effects of immune checkpoint blockade by anti‐CTLA‐4 and anti‐PD‐1 antibodies in metastatic melanoma

“…Other rare side effects include hematological abnormalities (erythrocyte aplasia, hemolytic anemia, pancytopenia), hemophilia , myopathy, myositis, and rhabdomyolysis. While ipilimumab has shown cardiac side effects such as cardiomyopathy , special attention is also warranted with respect to adverse events such as myocarditis and pericarditis. Myocarditis has repeatedly resulted in fatal outcomes .…”

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

“…Thus, serious side effects such as cardiotoxicity are still being documented. Nevertheless, clinical cardiotoxicity induced by ICIs and CART have been reported (Table ).…”

“…To date, FDA‐approved ICIs include Ipilimumab (CTLA‐4), Pembrolizumab (PD‐1), Nivolumab (PD‐1), Atezolizumab (PD‐L1), Avelumab (PD‐L1), and Durvalumab (PD‐L1). Based on the working principles, ICI‐induced toxicity typically involves autoimmune disorders, including autoimmune myocarditis . The importance of ICIs in the heart has been addressed in preclinical data, and the data give some mechanistic insights into the clinical observations of autoimmune myocarditis .…”

“…Based on the working principles, ICI-induced toxicity typically involves autoimmune disorders, 28,54,555,557,559 including autoimmune myocarditis. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]93,550 The importance of ICIs in the heart has been addressed in preclinical data, and the data give some mechanistic insights into the clinical observations of autoimmune myocarditis. 560,561 In addition, although ICIs are an attractive concept in the therapeutic development of cancer treatment, many cancer patients do not respond to treatments with ICIs, partly because of the lack of tumor-infiltrating effector T cells [562][563][564][565] or primary or acquired resistance due to various mechanisms.…”