Multiple Myeloma (MM)
Conditions
Brief summary
Multiple myeloma patients can be treated with cell therapy, which uses some of their own modified white blood cells (T lymphocytes) to target a protein (BCMA, or B-cell maturation antigen) found on the surface of the myeloma plasma cells. These modified T lymphocytes are called CAR T cells (chimeric antigen receptor T cells). The long-term persistence of these modified lymphocytes, or CAR-BCMA, is a recognized indicator of a good response to treatment. This research aims to study certain markers related to CAR-BCMA cell persistence. This research will be carried out in collaboration with the Laboratory of Ischemia Reperfusion, Metabolism and Sterile Inflammation in Transplantation (IRMETIST) INSERM unit U1313, located at the University of Poitiers. The proposed project will contribute to better patient care in the field of oncology, by identifying immunological cellular markers predictive of an effective response to anti-cancer treatments and/or immunotherapeutic targeting.
Detailed description
Multiple myeloma data will be collected from initial diagnosis and relapses, treatments receive since initial diagnosis and the CAR-T therapy (start of CAR-T therapy, type of CAR-T, responder status). Before and up to 1 year after CART C Cells treatment, blood (7) and bone marrow (3) samples will be sent to a centralised laboratories to analyse immune cells, including CAR-BCMA cells, and measure the expression of certain proteins on their surface (CD95 and CD95L) and the serum-soluble CD95L protein.
Interventions
OTHERAdditional Bone Marrow cells and blood sampling
Additional Bone Marrow cells and blood sampling
Sponsors
Poitiers University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Prospective interventional study with minimal risks and constraints, descriptive, exploratory, non-randomized, longitudinal, single-center, basic research aim.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient aged 18 and over * Patient with Multiple Myeloma according to international recommendations, * Patient about to receive CAR-T cell therapy in accordance with the rules and authorizations in France.
Exclusion criteria
* Patients with severely impaired physical and/or psychological health, which, according to the investigator, may affect the participant's compliance with the study. * Simultaneous participation in another study with an ongoing exclusion period. * Individuals receiving enhanced protection, namely minors, pregnant and/or breastfeeding women, individuals deprived of their liberty by a judicial or administrative decision, individuals residing in a healthcare or social care facility, adults under legal guardianship, and finally, patients in emergency situations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TCF-1 transcription factor (MFI) expression level in circulating CD3+ T cells | up to 1 year | TCF-1 transcription factor (MFI) expression level in circulating CD3+ T cells at baseline and correlation with the percentage of CAR-BCMA+ T cells at different follow-up time points up to 1 year after CAR-BCMA treatment |
| TCF-1 transcription factor (MFI) expression level in correlation with the depth of the patient's response as defined by international guidelines (IMS/IMWG criteria) | Up to 1 year | TCF-1 transcription factor (MFI) expression level in correlation with the depth of the patient's response as defined by international guidelines (IMS/IMWG criteria) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stemness correlation with the persistence of CAR-BCMA lymphocytes and in the bone marrow at 3 months and 12 months after CAR-BCMA treatment | Up to 1 year | To determine whether stemness, reflected by the expression of the transcription factor TCF1 in T lymphocytes (CD3+) before apheresis and/or lymphodepletion, is correlated with the persistence of CAR-BCMA lymphocytes in the patient, in the bone marrow at 3 months and 12 months after CAR-BCMA treatment |
| Expression of membrane CD95 in peripheral blood | Up to 1 year | Identify the mechanisms of immune response homeostasis, reflected by the expression of membrane CD95L and early differentiation, interfering with the persistence of CAR-BCMA(+) T cells in peripheral blood at different time points over 12 months after CAR-BCMA treatment |
| Inflammatory profile of patients | Up to 1 year | To determine whether the inflammatory profile of patients, as determined by cytokine assays (sCD95L, IL-1β, IFN-γ, IL-6, IL-10, IL-15, and TNF-α) at each time point, is inversely correlated with the persistence of CAR-BCMA(+) T cells in the periphery and/or in the bone marrow |
Countries
France
Contacts
CONTACTARTHUR BOBIN
CONTACTSTEPHANIE NOEL
Outcome results
None listed