Immune checkpoint inhibitor myocarditis: a metagenomic investigation of infectious pathogens

Immune-checkpoint inhibitors (ICI) improve survival of cancer patients but can cause fulminant myocarditis often part of a general systemic myotoxicity, being a rare yet potentially fatal immune-related adverse event.1–4 Whether occult infection (e.g. viral or bacterial) contributes to ICI-myocarditis (ICI-M) is unknown. We conducted a prospective, single-centre cohort (Pitié-Salpêtrière hospital, Paris, France; NCT05454527). Between 2019 and 2024, 256 patients were referred for suspected ICI-M. Cases were adjudicated as definite ICI-M or refuted–ICI-M using modified Bonaca criteria, as recently described.2,5,6 Of 231 patients with a final diagnosis, blood/endomyocardial biopsy (EMB) derived metagenomic next-generation sequencing (mNGS)7 was missing in 25 (11%) because no sample was drawn (refusal, death before sampling) or owing to technical failure, leaving 206 patients (110 definite ICI-M, 96 non-ICI-M) for analysis (flow chart in Figure 1). Cancers (64% male, median age 72 years IQR [60–78]) were mainly lung or pleural (27%), cutaneous (26%), and kidney or urothelial (22%); 72% had metastatic disease and ≈78% received PD-1/PD-L1 monotherapy, of which almost half were combined with another anti-cancer class. The upper limit of normal (ULN) for high-sensitivity cardiac troponin-T (cTnT) was 14 ng/L.6