Determinants of the Response to BTK Degraders (BTKd) in Chronic Lymphocytic Leukemia

The aim of the REBELLE cohort - bio-collection is to collect samples from patients with Chronic Lymphocytic Leukemia candidates or those exposed to BTK degraders to evaluate the mechanisms of resistance to these new molecules. To do this, an additional blood or bone marrow sample to those planned in the context of patient care or a residual lymph node biopsy sample will be collected after signing consent.

Chronic Lymphocytic Leukemia (CLL) is a malignant hematological disease of B cells, primarily observed in older adults. Although it is classified among indolent hematological malignancies, CLL exhibits significant heterogeneity, both in terms of its biological characteristics and its disease progression and the therapeutic strategies employed. In patients requiring treatment, the disease can relapse. Until recently, immunochemotherapy remained the standard treatment for this disease, but the last decade has seen the emergence of oral targeted therapies, such as Bruton's tyrosine kinase inhibitors (BKT1s) and BCL-2 inhibitors (BCL-2 inhibitors), which have profoundly altered patient prognosis. While the introduction of these two classes of drugs has led to improved prognosis, a rare but significant subgroup of patients, known as "double refractory," has emerged. These patients, exposed to both BKT and BCL-2 inhibitors and who have become refractory to both treatments, have a poor prognosis. To overcome this problem of resistance, molecules targeting the degradation of the BTK protein (BTKd) are currently under development. The main investigator propose the creation of a cohort and a biobank of samples from CLL patients who are candidates for or have been exposed to BTKd, in order to study the mechanisms of response and resistance to these molecules.

Inclusion Criteria: * Patient with CLL candidates ou exposed to BTKd * Patient who has provided informed consent to participate in the study. * Patient covered by a social security health insurance plan Exclusion Criteria: * Minor patients. * Adults under guardianship. * Protected persons.