What is the most clinically significant endpoint for CAR-T therapeutic approach to achieve effective results for lymphoma patients: should we consider CAR-T cell therapy as a drug or as a therapeutic pathway?

What is the most clinically significant endpoint for CAR-T therapeutic approach to achieve effective results for lymphoma patients: should we consider CAR-T cell therapy as a drug or as a therapeutic pathway?

B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) are two type of blood cancer that affects B lymphocytes, which are a group of the so-called white blood cells. B lymphocytes are supposed to help to fight infections but when they're “sick” they tend to reproduce themselves in a rapid and wrong manner becoming cancerous cells. These cancerous cells can spread everywhere in the body and in the blood, causing different type of symptoms or disease. Among the available therapies to treat B-ALL and DLBCL there are chimeric antigen receptor (CAR) T-cell therapy. The names of two of these products are axicabtagene ciloleucel and tisagenlecleucel.In CAR T-cells therapy, other non-cancerous white blood cells, called T-lymphocytes, of patients are extracted and collected from the blood with a medical technique called leukapheresis. After extraction, these cells are modified in specialized labs and become drugs thanks the adding of substances. At this point they are called CAR T-cells and are injected back into the same patient (just one shot). CAR T-cells are made to be attracted by a specific substance present in cancer cells. When CAR T-cells bind to a cancer cells, human immune system activates rapidly to kill cancer cells. Between leukapheresis and CAR T-cell infusion several weeks can pass. Thus, the patient pathway of cure with CAR T-cells starts from leukapheresis not from drug administration (if the drug had not been prescribed for him/her, he/she would not have done the leukapheresis).It is important to know the number of patients who can be cured and who cannot with these therapies. In addition, unfortunately, some patients will not receive CAR T-cells even if they have already performed leukapheresis. To check if a drug works, the proportion of patients cured on the total of patients treated is calculated with no exception for CAR T-cells therapies. Another method is to calculate how much time a patient to whom CAR T-cells were prescribed remains free from disease or alive. Starting from the fact that the patient pathway of cure with CAR T-cells starts from leukapheresis not from drug administration as stated above, we believe that to really know if CAR T-cells work the proportion of cured patients (or the amount of time a patient remains without diseases or alive) must be posed in relation to the total of patients who underwent leukapheresis (whether or not they actually receive the drug). The most research published, assessed CAR T-cells benefits counting only patients who received the drug and not the total of patients who underwent leukapheresis with the intention to receive the drug itself (otherwise they would not have done the leukapheresis). In fact, this research did not consider that between leukapheresis and CAR T-cells many events that prevent the cure itself can happen. Therefore, consider only patients who actually received the drug may corrupt results.In our study we aim to understand if calculating again CAR T-cells benefits considering all the patients who underwent leukapheresis with the intention to receive CAR T-cells will change the results already published. The final goal is to provide physicians, researchers and patients the most complete and correct overview of this therapeutic approach.Thus, we'll produce an overview with data already calculated on the total of patients who received CAR T-cells and, for each research, we will calculate same results but on the total of patients who underwent leukapheresis. The referring researchers of each study were contacted and involved in our study.

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