Blinatumomab Expanded T-cells (BET) in Indolent Non-Hodgkin Lymphomas/Chronic Lymphocytic Leukemia

Non-Hodgkin CD20 + Indolent Lymphoma (iNHL) and Chronic Lymphatic Leukemia (CLL) are the most frequent neoplasms of B lymphocytes. They include various histologies (follicular NHL, marginal zone NHL and Lymphocytic NHL/ CLL) characterized by a chronic course and prolonged survival, but while patients with a limited disease could be cured, those with advanced disease or relapsed after localized radiation therapy are generally considered untreatable through standard treatments. The options for first-line therapy include the use of the FCR scheme, based on Fludarabine, Cyclophosphamide and Rituximab or the BR, with Bendamustine and Rituximab. Despite good results, treatment with these two regimens (FCR or BR) is associated with severe immunosuppression which worsens the immunological dysfunction already present at diagnosis in several patients. It has been shown previously that the adoptive transfer of ex vivo anti-CD3/CD28 co-stimulated autologous T cells can successfully accelerate a robust early recovery of T cells after autologous transplantation in multiple myeloma. These CD3/CD28 expanded T cells cannot however be used in NHLi and CLL due to the presence of contaminating tumor cells in the preparation. Polyclonal T cells can also be expanded in vitro in presence of Blinatumomab and recombinant human IL2 (rhIL2) and have been called BET (Blinatumomab-expanded T cells). They are a product of Advanced Therapeutic Medicinal Product (ATMP) composed of polyclonal CD8 and CD4 T cells that are still functional and devoid of contaminating CD19+ neoplastic cells. Based on these data, it was hypothesized that infusion of BET in patients with iNHL/CLL, after the first treatment line (with FCR or BR), could induce adequate immunological recovery.