Cited by 511Cancer Immunotherapy and BiomarkersChemotherapy-induced cardiotoxicity and mitigationCardiac tumors and thrombi

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Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy

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Heinzerling, Lucie, Ott, Patrick A., Hodi, F. Stephen, Husain, Aliya N., Tajmir-Riahi, Azadeh, Tawbi, Hussein, Pauschinger, Matthias, Gajewski, Thomas F., Lipson, Evan J., Luke, Jason J.·2016·Journal for ImmunoTherapy of Cancer

DOI 10.1186/s40425-016-0152-yPMC PMC4986340

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Abstract

Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune-mediated cardiotoxicity induced by checkpoint inhibitors has been reported in single cases with variable presentation, including myocarditis and pericarditis. Among six clinical cancer centers with substantial experience in the administration of immune-checkpoint blocking antibodies, eight cases of immune-related cardiotoxicity after ipilimumab and/or nivolumab/pembrolizumab were identified. Diagnostic findings, treatment and follow-up are reported. A large variety of cardiotoxic events with manifestations such as heart failure, cardiomyopathy, heart block, myocardial fibrosis and myocarditis was documented. This is the largest case series to date describing cardiotoxicity of immune-checkpoint blocking antibodies. Awareness, monitoring of patients with pre-existing cardiac disorders and prompt evaluation by the treatment team is essential. Treatment including application of steroids is critical for patient safety.

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Fig. 1 Histologic presentation of case 1. Endomyocardial biopsy shows interstitial fibrosis with some interstitial lymphocytes. Signs of hypertrophy are detectableCC BY · PubMed Central

Fig. 2 Histologic presentation of case 5. a H&E stain of the endomyocardial biopsy shows patchy lymphohistiocytic infiltrates associated with myocyte damage, diagnostic for lymphocytic myocarditis. b IHC stain for CD3 highlights in brown T cells within the inflammatory infiltrate (c) IHC stain for CD8 highlights in brown T cells within the inflammatory infiltrate (d) IHC stain for CD68 shows many histiocytes/macrophages within the myocardial inflammationCC BY · PubMed Central

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Authors: Heinzerling, L., Ott, P. A., Hodi, F. S., Husain, A. N., Tajmir-Riahi, A., Tawbi, H., Pauschinger, M., Gajewski, T. F., Lipson, E. J., & Luke, J. J.
Affiliations: Universitätsklinikum Erlangen (DE)
Dana-Farber Cancer Institute (US)
University of Chicago (US)
The University of Texas MD Anderson Cancer Center (US)
Paracelsus Medizinische Privatuniversität (DE)
Sidney Kimmel Comprehensive Cancer Center (US)
Corresponding author: Heinzerling, Lucie
ORCID: Heinzerling, Lucie
Ott, Patrick A.
Hodi, F. Stephen
Husain, Aliya N.
Tawbi, Hussein
Pauschinger, Matthias
Gajewski, Thomas F.
Lipson, Evan J.
Luke, Jason J.
Venue: Journal for ImmunoTherapy of Cancer
Publisher: BMJ
Published: 2016-08-16
Volume: 4
Issue: 1
Pages: 50-50
ISSN: 2051-1426 (ISSN-L)
DOI: 10.1186/s40425-016-0152-y
PMC: PMC4986340
OpenAlex: W2478478625
Cited by: 511
References: 37
Citations by year: 2026: 21 · 2025: 29 · 2024: 34 · 2023: 43 · 2022: 50 · 2021: 77 · 2020: 78 · 2019: 64 · 2018: 61 · 2017: 50 · 2016: 2
FWCI: 31.82
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion, cc-by)
Funders: Melanoma Research Alliance
Celldex Therapeutics
National Institutes of Health
Genentech
National Cancer Institute (K12CA139160)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
Keywords: immune-related cardiotoxicity, CTLA-4 blockade, anti-PD-1 therapy, immune checkpoint inhibitors, ipilimumab, nivolumab, pembrolizumab, myocarditis, pericarditis, heart failure, cardiomyopathy, myocardial fibrosis, atrioventricular block, corticosteroid therapy

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