Immune Checkpoint Inhibitor-Associated Myocarditis: Risk, Diagnosis, and Clinical Impact
<b>Background:</b> Immune checkpoint inhibitors (ICIs), such as anti-programmed death (PD)-1 and anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 agents, have revolutionized oncology but are associated with immune-related adverse events (irAEs). Among these, ICI-associated myocarditis (ICI-M) is a rare but life-threatening complication, with mortality rates ranging from 27% to 50%. <b>Objective:</b> This narrative review summarizes the pathogenesis, epidemiology, clinical presentation, diagnostic methods, and management strategies for ICI-induced myocarditis, specifically highlighting emerging biomarkers and immunosuppressive therapeutic approaches. <b>Results and Discussion:</b> ICI-M typically presents within the first 65 days of treatment and is significantly more frequent with combination therapies. Pathologically, it is characterized by myocyte necrosis and massive infiltration of cluster of differentiation (CD)4+ and CD8+ T-cells, often overlapping with myositis (irM/M). Diagnosis relies on a multimodal approach. Management requires immediate ICI cessation and initiation of high-dose corticosteroids as first-line therapy. For steroid-refractory cases, second-line options include mycophenolate mofetil (MMF), intravenous immunoglobulin (IVIG), and emerging therapies like abatacept and ruxolitinib. Rechallenge with ICIs after high-grade ICI-M must be approached with extreme caution by the multidisciplinary team (MDT). Emerging biomarkers and omics techniques hold promise for earlier diagnosis and risk stratification. <b>Conclusions:</b> ICI-M is a rare yet highly lethal cardiac complication demanding high clinical vigilance and timely diagnosis. Management hinges on an aggressive multidisciplinary approach, aiming to minimize toxicity while balancing oncological efficacy.
Authors
- Valeria Cetoretta (ORCID: https://orcid.org/0000-0002-2137-0188)
- Federica Ilardi (ORCID: https://orcid.org/0000-0002-3885-5093)
- Maria Concetta Pastore (ORCID: https://orcid.org/0000-0002-7223-141X)
- Alfredo Mauriello (ORCID: https://orcid.org/0000-0001-7060-6938)
- Alessandro Malagoli (ORCID: https://orcid.org/0000-0001-9119-4311)
- Anna Chiara Maratea
- M Cameli
- Adriana Correra
- Vincenzo Russo
- Matteo Lisi
- Rosangela Cocchia
- Antonello D’Andrea
Institutions
- University of Siena (IT)
- University of Verona (IT)
- Marche Polytechnic University (IT)
- Ospedali Riuniti di Foggia (IT)
- Ospedale "Santa Maria delle Croci" di Ravenna (IT)
- Istituto Nazionale di Fisica Nucleare, Sezione di Napoli (IT)
- Federico II University Hospital (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Ospedali Riuniti Umberto I (IT)
- National Operating Committee on Standards for Athletic Equipment (US)
Publication Details
- Journal
- Journal of Clinical Medicine
- Published
- 2026-01-19
- DOI
- https://doi.org/10.3390/jcm15020814
- Citations
- 1
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 24.20