How can we manage the cardiac toxicity of immune checkpoint inhibitors?

ABSTRACT

Introduction: Cancer immunotherapies with monoclonal antibodies (mAbs) against immune checkpoints (i.e. CTLA-4 and PD-1/PD-L1) have revolutionized antineoplastic treatments. Immune checkpoint inhibitors (ICIs) approved for cancer immunotherapy are mAbs anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab, and cemiplimab), and anti-PD-L1 (atezolizumab, avelumab, and durvalumab). Treatment with ICIs can be associated with immune-related adverse events (irAEs), including an increased risk of developing myocarditis. These findings are compatible with the observation that, CTLA-4, PD-1, and PD-L1 pathways play a central role in the modulation of autoimmunity.

Areas covered: In this paper, we start from examining the pathogenesis of cardiovascular adverse events from ICIs, and then we focus on risk factors and strategies to prevent and manage this cardiotoxicity.

Expert opinion: There is a growing need for a multidisciplinary approach of ICI-associated cardiotoxicity, involving oncologists, cardiologists, and immunologists. Prevention and effective management of ICIs cardiotoxicity starts with an in-depth screening and surveillance strategies of high-risk patients, in order to improve early detection and appropriate management in a personalized approach.

KEYWORDS:

• Cancer
• cardiac toxicity
• immune checkpoint inhibitors
• immune-related adverse events

Article highlights

• Immune checkpoint inhibitors can be associated with immune-related adverse events (irAEs), including an increased risk of developing cardiotoxicity.

• Management of ICI cardiotoxicity requires multidisciplinary approach involving oncologists, cardiologists, and immunologists.

• In-depth screening and surveillance strategies are needed for early detection and appropriate management of cardiac irAEs in a personalized approach.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Prof. Gianni Marone, MD, for his invaluable intellectual suggestions, and Dr. Gjada Criscuolo for excellent secretarial help.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

MR Galdiero is supported, in part, by a grant from the Italian Ministry of Education, University and Research (MIUR). CM Della Corte declares an advisory board position for MSD, out of the present study. F Morgillo has received research grants from Astra Zeneca and has an advisory board position for MSD and Lilly. T Troiani received funding from Amgen, MSD, Novartis, Sanofi, BMS. CG Tocchetti has received research funding from Amgen; has received compensation from Alere for service as a consultant; and is listed as an inventor on two heart failure patents. V Mercurio has received research funding from MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.