Genetic Determinants of Myocarditis Induced by Immune-checkpoint Inhibitors

Status: Recruiting
Location: See location...
Study Type: Observational
SUMMARY

Immune checkpoint inhibitors (ICI) are active in multiple cancers. Their main drawback is the incidence of immune related adverse events; among which ICI-myocarditis (ICIM) is rare but can be the most life-threatening (up to 50% lethal). ICIM is due to ICI unleashing cytotoxic auto-reactive T-cells recognizing a culprit target antigen located on muscles and destroying them. Most often, ICIM occurs within a systemic ICI-myotoxicity, with peripheral muscular involvement (ICI-myositis), mimicking eventually myasthenia-gravis syndrome. Human Leukocyte Antigen (HLA) are cell surface proteins key for the regulation of the immune system acting via presentation of culprit antigens by antigen presenting cells (macrophages) to T-cells, subsequently triggering the destruction/tolerance of cells carrying this antigen. The HLA system (chromosome 6) is the most polymorphic region in the human genome and is associated with auto-immunity including myocarditis. HLA class I alleles have been strongly associated with some T-cell-mediated drug hypersensitivity reactions with handful patients needed to be tested to prevent a single case, leading to globally required cost-effective HLA typing pre-prescription for some drugs.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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).

• Signature of informed consent before any trial procedure from the patient

• Patients covered by social security regimen (excepting AME).

Locations
Other Locations
France
Hôpital Pitié Salpêtrière
RECRUITING
Paris
Contact Information
Primary
Joe Elie SALEM, Pr
joe-elie.salem@aphp.fr
01 42 17 85 35
Time Frame
Start Date: 2025-09-23
Estimated Completion Date: 2028-07-20
Participants
Target number of participants: 500
Treatments
ICI-tolerant patients without suspicion of myotoxicity (Controls)
300 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 new cardio-muscular symptoms or ECG abnormality or wall motion abnormality or troponin-T increase (above Upper Limit of Normal if normal prior to ICI start, or over twice its troponin-T baseline value if abnormal before ICI start)
Patients with refuted suspicion of ICI-myocarditis (controls)
100 Cancer patients treated with ICI and with definite ICI-induced myocarditis according to last updated diagnostic criteria's
ICI-Myocarditis Cases (Cases)
100 Cancer patients treated with ICI admitted for a suspicion of ICI-myocarditis subsequently infirmed
Related Therapeutic Areas
Sponsors
Leads: Assistance Publique - Hôpitaux de Paris

This content was sourced from clinicaltrials.gov