[Pubmed] Incidence and risk factors of immune checkpoint inhibitor myocardial and muscle toxicity: a French nationwide s

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Eur Heart J. 2025 Aug 30:ehaf682. doi: 10.1093/eurheartj/ehaf682. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Immune checkpoint inhibitor (ICI)-induced (cardio)-myotoxicities, including myocarditis and myositis, are uncommon but frequently severe adverse drug reactions seen in cancer patients. Real-life ICI myotoxicity incidence estimates span from limited-size cohorts, with risk factors and prognosticators poorly established, as well as their impact on survival.

METHODS: This retrospective French National Health Data System cohort study included all adult patients starting ICI between 1 January 2012 and 30 September 2022. A 'narrow' and a 'broad' code combination (based on International Classification of Diseases-10 codes) were used for studied outcomes. The primary outcome was the occurrence of myotoxicities and secondary outcomes of myocarditis and myositis. Risk factors of these outcomes at 6 months were identified with Fine and Gray multivariable models, considering demographics, comorbidities, co-treatments, and cancer. Immune checkpoint inhibitor myotoxicity (as a time-dependent variable) association with overall survival was tested using Cox models. Risk factors of 1- and 3-month letality in ICI myotoxicity cases were assessed by multivariable logistic regression.

RESULTS: In 172 363 ICI-treated adult patients, incidence of ICI myotoxicities at 6 months ranged between 0.7% and 0.9% (narrow or broad definitions, respectively), with up to 7.1% in patients with thymic cancer. Immune checkpoint inhibitor myocarditis and ICI myositis incidence ranged between 0.3% and 0.6%, co-occurring in ∼13%-23% of cases. The main risk factors for developing ICI myotoxicities (broad, n = 1520) were thymic tumour (sub-distribution hazard ratio [sHR] 12.94, 95% confidence interval [CI] 5.22-32.03), melanoma (2.41 [2.06-2.83]) and other skin cancers (2.07 [1.55-2.76]), history of thymic disorders (5.61 [2.66-11.86]), history of myasthenia gravis (2.50 [1.45-4.32]), combination of ICI (2.44 [1.99-2.98]), and age > 85 [1.79 [1.24-2.59] vs 170 000 French patients treated by ICI in real life, establishing the incidence and identifying risk factors of developing ICI myotoxicities, with severity surrogates associated with fatality.

PMID:40884033 | DOI:10.1093/eurheartj/ehaf682


Source: https://pubmed.ncbi.nlm.nih.gov/4088403 ... t9+e462414