A treatment based on cells modified by gene therapy, recently authorized in the United States, is proving to be very effective in young people with acute lymphoblastic leukemia, especially in relapse. And this, despite significant side effects.
Last year, the FDA, the US drug agency, gave the green light to a treatment: Kymriah (tisagenlecleucel), developed by the laboratory Novartis. To conduct their research, scientists around the world looked at children and young adults with acute lymphoblastic leukemia, who had recurred or were resistant to previous treatments. The results of the study, published in the New England Journal of Medicine, shows the additional chances of remission given by the Kymriah.
Gene therapy treatment
Kymriah is the first treatment using certain patient’s white blood cells modified by gene therapy authorized in the United States. Concretely, it is based on “CAR-T cells”, that is to say genetically reprogrammed cells. Doctors take cells of the immune system from the patient’s white blood cells, these are T lymphocytes. These lymphocytes are then modified by gene therapy to make them express a receptor directed against a protein present on the surface of leukemia cells, the CD- 19. This modification of the patient’s cells is obtained thanks to a special virus which will incorporate into these lymphocytes a DNA fragment capable of synthesizing this CD-19 receptor. Then the modified lymphocytes (CAR-T cells or CD-19 T lymphocytes) are multiplied, then reinjected into the patient.
81% remission rate
In this study, the researchers carried out the modified T lymphocytes in a center in the United States then in another in Europe, and treated the young patients with their own modified cells in 25 centers scattered around the world.
They analyzed the overall remission rate, following an injection of Kymriah, in the following three months. The result: an overall remission rate within three months of 81%.
Watch out for side effects
While the results of the study bear witness to the efficacy of the treatment, Kymriah, by attacking the numerous leukemia cells, causes side effects which can be severe. 73% of patients analyzed had side effects likely to be related to therapy, of which 30% required intensive care to control cytokine release syndrome, also called “cytokine shock”. This syndrome can now be better treated with anti-IL6 antibodies.
A fatal risk
The patient’s immune cells destroy cancer cells that carry CD-19. This releases molecules: cytokines. In too large a quantity, they cause effects generally close to the flu-like state, therefore benign. But it can be more serious, for example with a drop in blood pressure, kidney problems or even a decrease in oxygen in the blood. According to the FDA, cytokine shock can be fatal. Patients must therefore be followed very closely.
CAR-T cells, a tailor-made treatment, represent a formidable advance but are very expensive, both for their preparation, but also for the management of the treatment. Their efficacy has been demonstrated in leukemia, in lymphoma, in myeloma and in certain solid tumors.
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