Is Trogocytosis a Predictive Marker of CAR-T Cell Response in Diffuse Large B-cell Lymphoma?

La Trogocytose Est-elle un Marqueur prédictif de la réponse Aux Cellules CAR-T Dans Les Lymphomes Diffus à Grandes Cellules B ?

CAR-T cell therapy has improved survival in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL R/R). However, only 65% of patients achieve a complete metabolic response after this treatment. To date, there is no predictive test for therapeutic response after injection of CAR-T cells. Recent studies have shown that the level of trogocytosis by immune cells correlates with the persistence of tumor cells in patients with hematological malignancies. Our main objective is to identify a phenotypic "signature" of trogocytosis predictive of therapeutic response 6 months after injection of CAR-T cells for DLBCL.

The therapeutic use of CAR-T cells (Chimeric Antigen Receptor T-cells) has significantly improved the survival of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, only 65% of patients achieve metabolic complete response after this treatment, and one year after CAR-T cells infusion, between 50 and 60% of patients have relapsed or died. Injection of CAR-T cells can also be responsible for serious immunologic and hematologic adverse events. To date, there is no predictive test for the therapeutic response or toxicity following injection of CAR-T cells.

Trogocytosis is a physiological mechanism by which an effector immune cell integrates fragments of the membrane of target cells into its membrane. These aberrant membrane markers can directly modify the functions of the cell that has acquired them. Although the physiological role of trogocytosis remains debated, recent studies have shown that the level of trogocytosis in immune effector cells is correlated with persistent tumor cells in patients with hematological malignancies.

Our main hypothesis is that, in DLBCL, the level of early trogocytosis, assessed by the aberrant expression of tumor markers on the surface of CAR-T cells and other immune effector cells between D0 and D30 after CAR-T cells infusion, correlates with therapeutic response at M6 and/or the occurrence of immunological or severe hematological CAR-T cells side-effects.

Inclusion Criteria:

• For patients

  • Patient who has given free and informed consent in writing for inclusion in the non-interventional CART-BANK protocol, and orally for the CARTROG protocol,
  • Patients over 18 years of age at the time of inclusion,
  • Diagnosis of LDGCB,
  • Decision to treat with anti-CD19 CAR-T cells,
  • Patient affiliated to or benefiting from a social security scheme.

• For healthy volunteers:

  • Given free and informed oral consent for inclusion in the CARTROG protocol,
  • Donor between 18 and 70 years of age at the time of inclusion,
  • No history of solid cancer or hematological malignancy,
  • No known chronic pathology (e.g. hypertension, diabetes, etc.) and no daily treatment,
  • No surgical treatment within the last 6 months.

Exclusion Criteria:

• Patients who do not meet all the inclusion criteria,
• Pregnant or breast-feeding patient,
• Patient unable to follow the procedures and/or frequency of visits planned in the trial, for psychological, family, social or geographical reasons,
• Patient unable to consent freely to inclusion, under guardianship, curatorship or safeguard of justice.