Innate T Cells and TKI Discontinuation

Innate T-cells as a Biomarker of Successful TKI Arrest in Chronic Myeloid Leukemia

After more than a decade of treating chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI), the discontinuation of treatment represents the expected new revolution. The investigators has recently discovered a new innate CD8+ T population in healthy subjects, the Eomes+ KIR+ CD8+ T population, with anti-tumor properties. Remarkably, these cells are numerically and functionally deficient in patients at diagnosis and then restored in patients in major molecular remission (MMR) on TKI. Our work performed in a retrospective pilot study interestingly shows a very significant increase in the proportion of CD8+ Eomes+ KIR+ T cells within total T cells in patients with prolonged success in stopping their ITK (≥ 2 years).Thus, the investigators postulate that CD8+ Eomes+ KIR+ T cells are a predictive signature of TKI arrest success in CML. The investigators will rely on a prospective translational study of this cell contingent during treatment cessation.

To perform this research, the investigators have started a prospective translational study to collect samples in CML patients with successful versus patients who have failed TKI therapy discontinuation. The investigators plan to study functional and phenotypic characteristics of innate T cells. The investigators also plan to evaluate in vitro whether immune check points inhibitors could help to restore the innate T lymphocytes population.

Inclusion Criteria:

• Age > 18 years old
• Diagnosis of CML-PC according to the criteria of the European Leukemia Net (Baccarani et al, 2013)
• Patients treated with TKI for at least 3 years (imatinib, nilotinib, dasatinib, bosutinib, ponatinib)
• Patients meeting the criteria of the French STIM study: deep molecular response of MR4.5 type (threshold of 0.0032%) or MR5 type (threshold of 0.001%) for at least 2 years,
• Free subject, without guardianship or curatorship or subordination
• Patients benefiting from a Social Security system or benefiting from it through a third party

Exclusion Criteria:

• Refusal to participate in the research
• Patients not benefiting from a Social Security scheme or not benefiting from it through a third party
• Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies
• Patient having stopped treatment for another reason than: deep molecular response of MR4.5 (threshold of 0.0032%) or MR5 (threshold of 0.001%) for at least 2 years

Translated with www.DeepL.com/Translator (free version)