Genetic factors linked to myocarditis from immune‑checkpoint inhibitor treatment

Genetic Determinants of Myocarditis Induced by Immune-checkpoint Inhibitors

We will test whether certain genes, especially HLA types, are linked to myocarditis in adult cancer patients treated with immune‑checkpoint inhibitors.

Quick facts

• Study type: Observational
• Enrollment: 500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris)
• Trial ID: NCT06734689 on ClinicalTrials.gov

What this trial studies

This observational project collects clinical data and blood samples from cancer patients treated with immune‑checkpoint inhibitors to search for genetic markers associated with ICI‑myocarditis. Investigators will compare HLA alleles and other genetic variants between patients who develop myocarditis and matched patients on ICI without new cardio‑muscular symptoms, and an MRI sub‑study will provide detailed cardiac imaging where possible. Samples will undergo HLA typing and genomic analyses while clinical information (ECG, troponin, imaging, and symptom data) is recorded. The goal is to identify genetic risk markers that could help predict which patients are most vulnerable to severe immune‑related cardiac toxicity.

Who should consider this trial

Good fit: Adults (≥18) with cancer who have received at least two doses of an immune‑checkpoint inhibitor and who have no new cardiac or muscular symptoms compared with their pre‑ICI baseline, can provide informed consent, and are covered by social security are ideal candidates.

Not a fit: Patients who already have ICI‑myocarditis, are under 18, pregnant or breastfeeding, legally protected adults, or those unable to consent or undergo required procedures (such as MRI for the sub‑study) are unlikely to directly benefit from participation.

Why it matters

Potential benefit: If successful, this work could identify genetic markers to predict high risk of life‑threatening ICI‑myocarditis and guide closer monitoring or alternative therapy choices.

How similar studies have performed: HLA associations have been reported in autoimmune myocarditis and other immune toxicities, but genetic predictors specific to ICI‑myocarditis are not yet well established.

Eligibility criteria

Inclusion Criteria:

1. Cancer patients on ICI since at least 3 months with a minimum of 2 ICI doses received having no appearance (as compared to baseline known pre-ICI) of a new cardio-muscular symptoms or ECG abnormality or WMA or troponin-T increase (above ULN if normal prior to ICI start, or over twice its troponin-T baseline value if abnormal before ICI start).
2. Signature of informed consent before any trial procedure from the patient
3. Patients covered by social security regimen (excepting AME).

Exclusion Criteria:

1. Age \<18 years of age.
2. Pregnant or breast-feeding women
3. People under legal protection measure (safeguard measures)

Specific exclusion criteria for the magnetic resonance imaging sub-study (MRI)

* Patients with a contraindication to MRI (claustrophobia, some wearing equipment with magnetic properties: pacemaker, ferromagnetic equipment, etc.)
* Intolerance to gadolinium, or severe renal insufficiency (GFR\<30 ml/min/1.73 m2).

Of note, the other groups of patients needed to complete this study; i.e the patients with refuted suspicion of ICI-myocarditis who will serve as controls, and the patients with ICI-myocarditis (cases) are included in another protocol (NCT05454527)

Where this trial is running

Paris

• Hôpital Pitié Salpêtrière — Paris, France (Recruiting)

Study contacts

• Principal investigator: Joe Elie SALEM, Pr — Assitance Publique - Hôpitaux de Paris
• Study coordinator: Joe Elie SALEM, Pr

Conditions ICI-myocarditis; Myocarditis; Myositis; Immune-checkpoint inhibitors; Pharmacogenetic