CAR-Modified T-Cell Therapy As Potential New Treatment For Non-Hodgkin Lymphomas

CAR-Modified T-Cell Therapy As Potential New Treatment For Non-Hodgkin Lymphomas

Results of a new study entitled “Phase II trial of chimeric antigen receptor modified T cells directed against CD19 in relapsed/refractory diffuse large B cell, follicular, and mantle cell lymphomas were recently presented during the 13th International Conference on Malignant Lymphoma, in Lugano, Switzerland.

Lymphomas are the most common type of blood cancer and occur when cells of the immune system start to proliferate uncontrollably. Bcell lymphomas are a type of lymphoma that affects immune B cells, which are identified by a specific biomarker, the CD19 protein.

In this study, researchers enrolled patients with CD19-positive B cell lymphomas who had no treatment options. Additionally, the study included patients with particular types of lymphomas – mantle cell (MCL) and follicular lymphoma (FL), the former a rare B-cell non-Hodgkin’s lymphoma (NHL) and the latter the second-most-common form of NHL.

Patients were treated with a chimeric antigen receptor (CAR)-modified T-cell therapy directed against CD19, known as CTL019 and composed of T cells that carry an artificial receptor. In this case, researchers engineered T cells to express the receptor for CD19, allowing them to bind exclusively to CD19 expressing B cells.

This technique retrieves T cells from a patient and modifies them to express receptors specific for a particular form of cancer, in this case, to express the CD19 receptor. T cells are then reintroduced back into the patient so that they can target and kill cancerous CD19-expressing B cells.

Patients with CD19-positive diffuse large B-cell lymphoma exhibited an overall response rate (ORR) of 46% (measured at 3 months of treatment) and a median progression-free survival (PFS) of 90 days; the MCL cohort exhibited an ORR of 50% and remained ongoing at 50 days, while FL patients’ ORR was of 100%.

Stephen J. Schuster, MD, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania commented, “The response is very rapid and we can tell very quickly during the first weeks if the cells are working. CTL019 chimeric antigen receptor modified T cells directed against CD19 can achieve durable responses in patients with relapsed or refractory CD19-posititive diffuse large B-cell and follicular lymphomas; it is too early to make a conclusion regarding the patients with mantle cell lymphoma.”

CTL019 is being developed as a collaboration between the University of Pennsylvania and Novartis and researchers will continue to perform additional studies with CTL019 in lymphomas but also in other hematologic malignancies.

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