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Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

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Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

continued treatment with TKI at 50% dose reduction compared to dosing received at randomization and then stopped treatment 12 months after randomization

continued treatment with TKI at same dose compared to dosing received at randomization and then stopped treatment 12 months after randomization

continued treatment with TKI at randomization a then stopped treatment 12 months after randomization

treatment of TKI in CML

Emilie Cayssials-Caylus, Dr

Corentin ORVAIN, Dr

Fréderic BAUDUER, Dr

Jean Christophe IANOTTO, Dr

Lydia ROY, Dr

Emmanuel FLECK, Dr

Valerie COITEUX, Dr

Amélie PENOT, Dr

Franck NICOLINI, Dr

Samia MADENE HAROUNE, DE

Viviane DUBRUILLE, Dr

José Miguel TORREGROSA DIAZ, DR

Claire CALMETTE, Dr

Francoise HUGUET, Dr

Antoine MACHET, Dr

Philippe ROUSSELOT, Dr

Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack of cure, is frequently associated with moderate, chronic and sometimes severe adverse effects. The ability to permanently stop treatment with TKI has thus become a major goal in CML to prevent the occurrence of adverse events, improve quality of life and reduce the general cost of the treatment; we talk about Treatment Free Remission (TFR). It now remains to be demonstrated in a comparative prospective study that a strategy of de-escalation of the TKI treatment dose before treatment discontinuation optimizes TFR results. At the same time, it is possible to reduce adverse reactions and improve the quality of life of patients. In this context, the investigator propose to conduct a randomized clinical trial including CML patients, allowing to compare the results of TFR at 24 months between a sudden stop of treatment after a maintenance phase of dosage for 12 months and a de-escalation arm of dose (dosage reduced by 50%) for 12 months before stopping. A secondary immunological translational objective of this project will be to compare the quantitative and qualitative evolution of innate CD8 T cells between the 2 arms (abrupt cessation of ITK treatment versus progressive withdrawal) and look for a predictive innate CD8 T cells blood signature at the time of stopping treatment of a successful TFR in both arms.

Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System

Discontinuation of TyrosIne Kinase Inhibitors (ITK) in Chronic Myeloid Leukemia (LMC) and Impact on the Immune System: a Randomized Comparative Study of Two Therapeutic Strategies

Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL level ≤ 0.1% IS) on the total number of patients.

Poitiers University Hospital

Heart and Blood Diseases

Heart Arrest

functional and phenotypic characteristics of innate T cells

Characteristics of innate T cells

Emilie CAYSSIALS

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.

Innate T Cells and TKI Discontinuation

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

Proportion of the CD8+ Eomes+ KIR+ T cells among CD8+ T cells between patients in failure versus those in success after discontinuation of TKI treatment

Phenotypic markers expression : CD49d, CD57, CD45RA et CCR7, CD25 et HLA-DR among total CD8+ T cells

Functionality of LT CD8+ Eome+ KIR+ : expression of perforin and IFNgamma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System	NCT05753384	Tyrosine Kinase... Chronic Myeloid...	treatment of TK...	18 Years -	Poitiers University Hospital
Innate T Cells and TKI Discontinuation	NCT04645706	Chronic Myeloid...	Characteristics...	18 Years - 100 Years	Poitiers University Hospital

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