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. 2023 Apr 20;16(4):625.
doi: 10.3390/ph16040625.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

Danielle Delombaerde  1   2 , Johan De Sutter  3   4 , Lieselot Croes  1   2 , Delphine Vervloet  3 , Veronique Moerman  3 , Nico Van de Veire  3   5 , Anne-Marie Willems  3 , Kristien Wouters  6 , Marc Peeters  2   7 , Hans Prenen  2   7 , Christof Vulsteke  1   2
Affiliations

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

Danielle Delombaerde et al. Pharmaceuticals (Basel). .

Abstract

Background: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting.

Methods: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem.

Trial registration: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

Keywords: biomarker; cardiac troponin; cardio-oncology; cardiotoxicity; diastolic function; immune checkpoint inhibitor; immune-related adverse event; myocarditis; subclinical cardiotoxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study flow. Abbreviations: CT, computed tomography; ECG, electrocardiogram; Hs-TnI, high-sensitivity troponin I; hs-TnT, high-sensitivity troponin T; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; NT-proBNP, N-terminal pro-B-type natriuretic peptide; sAE, severe adverse event; SOC, standard of care.
See this image and copyright information in PMC

References

    1. Wang D.Y., Okoye G.D., Neilan T.G., Johnson D.B., Moslehi J.J. Cardiovascular Toxicities Associated with Cancer Immunotherapies. Curr. Cardiol. Rep. 2017;19:21. doi: 10.1007/s11886-017-0835-0. - DOI - PMC - PubMed
    1. Jain V., Bahia J., Mohebtash M., Barac A. Cardiovascular Complications Associated with Novel Cancer Immunotherapies. Curr. Treat. Options Cardiovasc. Med. 2017;19:36. doi: 10.1007/s11936-017-0532-8. - DOI - PubMed
    1. Wang D.Y., Salem J.-E., Cohen J.V., Chandra S., Menzer C., Ye F., Zhao S., Das S., Beckermann K.E., Ha L., et al. Fatal Toxic Effects Associated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4:1721–1728. doi: 10.1001/jamaoncol.2018.3923. - DOI - PMC - PubMed
    1. Michel L., Rassaf T., Totzeck M. Cardiotoxicity from immune checkpoint inhibitors. IJC Heart Vasc. 2019;25:100420. doi: 10.1016/j.ijcha.2019.100420. - DOI - PMC - PubMed
    1. Escudier M., Cautela J., Malissen N., Ancedy Y., Orabona M., Pinto J., Monestier S., Grob J.J., Scemama U., Jacquier A., et al. Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation. 2017;136:2085–2087. doi: 10.1161/CIRCULATIONAHA.117.030571. - DOI - PubMed

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