Late-Onset Fulminant Myocarditis With Immune Checkpoint Inhibitor Nivolumab

Yamaguchi, Shogo; Morimoto, Ryo; Okumura, Takahiro; Yamashita, Yuta; Haga, Tomoaki; Kuwayama, Tasuku; Yokoi, Tsuyoshi; Hiraiwa, Hiroaki; Kondo, Toru; Sugiura, Yuki; Watanabe, Naoki; Kano, Naoaki; Kohno, Kei; Fukaya, Kenji; Sawamura, Akinori; Yokota, Kenji; Ishii, Hideki; Nakaguro, Masato; Akiyama, Masashi; Murohara, Toyoaki

doi:10.1016/j.cjca.2018.03.007

Cited by 62 publications

(46 citation statements)

References 5 publications

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“…In a report 11 of pembrolizumab-treated patients with Merkel cell carcinoma, 1 patient had myocarditis. Myocarditis in the monotherapy setting has also been reported in the treatment of non-small cell lung cancer, including both adenocarcinoma and squamous cell carcinoma 12-14 and melanoma, 15,16 some patients with fatal outcome and others with recovery from myocarditis.…”

Section: Discussionmentioning

confidence: 99%

Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy

Sobol

Chen

Mahmood

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Cardiac complications of immune checkpoint inhibitor therapy are rare, but reports of myocarditis are increasing. The findings have been described in case reports as lymphocytic myocarditis, but its histopathology is underreported. Objective.— To review the histology of myocardial biopsy–proven cases of immune checkpoint–associated myocarditis and provide immunohistochemical characterization of the inflammatory infiltrate. Design.— We have encountered 6 patients with biopsy-proven myocarditis in conjunction with therapy using anti–programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) agents with and without cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors and characterized the histopathology and immune cell profile. Results.— The myocarditis was multifocal/diffuse, and characterized by a predominant CD163-positive histiocytic infiltrate, with an associated CD8+ and PD-1+ T-lymphocytic infiltrate, some of which were granzyme B positive. Cardiac myocytes showed immunoreactivity for PD-L1 in areas of injury, confirmed using 2 different anti–PD-L1 clones. Four of 6 patients recovered from their cardiac injury. One patient had residual tachycardia-bradycardia syndrome and 1 patient expired. Conclusions.— The diffuse lymphohistiocytic myocarditis associated with this therapy is relatively distinctive, and this diagnosis is strongly suggested based on the histopathologic findings in the correct clinical setting.

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Section: Discussionmentioning

confidence: 99%

Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy

Sobol

Chen

Mahmood

2020

Archives of Pathology &Amp; Laboratory Medicine

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“…In contrast, a patient with melanoma had been reported to develop pericarditis 3 months after four cycles of ipilimumab (Yun et al, 2015). Interestingly, patients without any obvious symptoms had been found to have fulminant myocarditis after 1 year of ICI treatment (Yamaguchi et al, 2018). We reviewed previously published cases of adverse cardiac reactions and found that the onset time of cardiotoxicity was earlier in the combination of two ICIs.…”

Section: Incidence and Clinical Manifestations Of Immune Checkpoint Imentioning

confidence: 99%

Immune Checkpoint Inhibitor-Associated Cardiotoxicity: Current Understanding on Its Mechanism, Diagnosis and Management

et al. 2019

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Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte antigen 4, programmed cell death-1, and PD-ligand 1 have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. ICIs are increasingly being used in early cancer settings and in combination with various other types of therapies, including targeted therapy, radiotherapy, and chemotherapy. However, despite the excellent therapeutic effect of ICIs, these medications typically result in a broad spectrum of toxicity reactions, termed immune-related adverse events (irAEs). Of all irAEs, cardiotoxicity, uncommon but with high mortality, has not been well recognized. Herein, based on previous published reports and current evidence, we summarize the incidence, diagnosis, clinical manifestations, underlying mechanisms, treatments, and outcomes of ICI-associated cardiotoxicity and discuss possible management strategies. A better understanding of these characteristics is critical to managing patients with ICI-associated cardiotoxicity.

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“…Cardiovascular toxicities are among the rare organ toxicities of ICI therapy [5, 6]. With increased use of ICIs over the past few years, numerous reports of cardiovascular toxicities have emerged (summarized in Table 1, Table 2, Table 3) [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35]. The most serious among them is the development of fulminant myocarditis, a potentially fatal clinical disease which has been the primary focus for the cardio-oncology community [12].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

Agrawal¹,

et al. 2019

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The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced stage cancers. However, immune-related adverse events are frequently observed. Cardiac toxicity from ICI therapy can range from asymptomatic troponin-I elevations to conduction abnormalities of the heart and even fulminant myocarditis. Although rare, myocarditis is a potentially fatal adverse effect of ICI therapy. We present a series of five cases of ICI-related cardio-toxicity diagnosed and managed at Roswell Park Comprehensive Cancer Center along with a review of published case reports in the literature. Our series highlights the importance of high clinical suspicion, early diagnosis of myocarditis, and prompt initiation of immunosuppressive therapy.

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Late-Onset Fulminant Myocarditis With Immune Checkpoint Inhibitor Nivolumab

Cited by 62 publications

References 5 publications

Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy

Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy

Immune Checkpoint Inhibitor-Associated Cardiotoxicity: Current Understanding on Its Mechanism, Diagnosis and Management

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

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