Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Oct;23(10):1739-1747.
doi: 10.1002/ejhf.2289. Epub 2021 Jul 29.

Cardiotoxicity associated with immune checkpoint inhibitor therapy: a meta-analysis

Nestor Rubio-Infante  1 , Yoel A Ramírez-Flores  1 , Elena C Castillo  1 , Omar Lozano  1   2 , Gerardo García-Rivas  1   2   3 , Guillermo Torre-Amione  1   2   4
Affiliations
Free article
Meta-Analysis

Cardiotoxicity associated with immune checkpoint inhibitor therapy: a meta-analysis

Nestor Rubio-Infante et al. Eur J Heart Fail. 2021 Oct.
Free article

Abstract

Aims: This study aimed to estimate the incidence of cardiac immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs).

Methods and results: First, we performed an ICI pharmacovigilance analysis, finding 4.2% of cardiac disorders, including myocarditis, for anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapies. Patients treated with anti-PD-1 antibodies presented a greater number of cardiac adverse events (AEs) than those treated with anti-CTLA-4 (69.4% vs. 20%). Then, we analysed the incidence and characteristics of cardiac irAEs in 1265 papers published prior to 31 August 2020. Of the 4751 patients studied, 1.3% presented cardiac irAEs, with myocarditis being the most frequent (50.8%); 15 patients died (24.6%) due to cardiac irAEs. Finally, we conducted a meta-analysis to determine cardiac irAEs in randomized clinical trials, identified through a systematic search from the ClinicalTrials.gov database, finding an incidence of 3.1% for ICI monotherapies, 5.8% for dual ICI therapies, 3.7% (irAEs/AEs) for ICIs plus chemotherapy, and cardiac AEs were reported in 2.5% of patients treated solely with chemotherapy.

Conclusions: Our study provides precise data for the incidence of cardiac irAEs among patients using ICIs, where despite its low incidence, the high rate of mortality is an important issue to consider. ICIs induce mainly myocarditis at the first doses, and dual therapies seem to provoke higher rates of cardiac irAEs than monotherapies or ICIs plus chemotherapy.

Keywords: Adverse events; CTLA-4; Cardiotoxicity; Immune checkpoint inhibitors; Myocarditis; PD-1.

PubMed Disclaimer

Comment in

References

    1. Franzin R, Netti GS, Spadaccino F, Porta C, Gesualdo L, Stallone G, Castellano G, Ranieri E. The use of immune checkpoint inhibitors in oncology and the occurrence of AKI: where do we stand? Front Immunol 2020;11:1-20.
    1. Sharma P, Siddiqui BA, Anandhan S, Yadav SS, Subudhi SK, Gao J, Goswami S, Allison JP. The next decade of immune checkpoint therapy. Cancer Discov 2021;11:838-857.
    1. Szuchan C, Elson L, Alley E, Leung K, Camargo AL, Elimimian E, Nahleh Z, Sadlery D. Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. Eur Heart J Case Rep 2020;4:1-8.
    1. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995;3:541-547.
    1. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995;270:985-988.

Publication types

Substances