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CAR-T Meeting 2021 | CAR T-cells in adult ALL

CD19-directed CAR T-cells have been approved for use in children and young adults up to the age of 25 years with acute lymphoblastic leukemia (ALL). Arnon Nagler, MD, Chaim Sheba Medical Center, Tel-Aviv, Israel, outlines the use of CAR T-cells in adult ALL. Several prognostic factors for CAR-T therapy’s success have been identified, including platelet count before CAR-T infusion, lactate dehydrogenase (LDH) level, and mutated p53. Additionally, Prof. Nagler discusses if CAR T-cells are the definitive therapy for ALL or a pathway to allogeneic transplant. Finally, Prof. Nagler shares new approaches for CAR T-cells in ALL, including CD22-directed CAR T-cells, sequential administration of CD19 and CD22 CAR T-cells, bispecific CARs, and allogeneic CAR T-cells. This interview took place during the 3rd European CAR T-cell Meeting.

Transcript (edited for clarity)

ALL was the first indication for an approval of CAR T-cells in young children and young adults up to the age of 25. I would say that this is also the disease in which we have the best success of CAR T-cells. So I will discuss the big studies both from Europe, from the States, and from China of CAR T-cells in adult ALL and about the efficacy and about the prognostic factors.

So we know today after a few years of therapy that there are several prognostic factors for success or CAR T-cell in adult ALL including the platelet count before giving the CAR T-cells and LDH, which is a factor of the disease...

ALL was the first indication for an approval of CAR T-cells in young children and young adults up to the age of 25. I would say that this is also the disease in which we have the best success of CAR T-cells. So I will discuss the big studies both from Europe, from the States, and from China of CAR T-cells in adult ALL and about the efficacy and about the prognostic factors.

So we know today after a few years of therapy that there are several prognostic factors for success or CAR T-cell in adult ALL including the platelet count before giving the CAR T-cells and LDH, which is a factor of the disease. And new data are coming about mutation on p53. It is also predicting response to CAR T-cells. And if the patient had in the past allogeneic extensive transplantation.

I devote quite a big part of my talk to whether we need to do allogeneic transplantation post CAR T-cells because this is crucial. Is the CAR T-cell a final therapy for ALL or is this just a pathway for allogeneic transplantation, bringing the patient to transplant in a better condition?

So there is controversies about this. Studies that show that the allogeneic transplant is not improving and is a response to CAR T-cells. Others show improved response, but there are more and more data including a paper that was published this year about more than 430 allogeneic transplant CAR T-cell solely in ALL showing this is a pooling of many studies showing that the relapse rate in patients that received allogeneic transplant after CAR T-cells are significantly lower than the relapse rate in patients that received CAR-T cells, achieved CR or in minimal disease negativity and didn’t receive a transplant. So the recommendation are that in patients that lose the CAR T-cells fast or did not have a previous allogeneic transplant we should offer them CAR T-cells.

And then, a bit about the toxicity. Starting earlier with the tocilizumab and even giving a low dose of steroids. And a new approach is for CAR T-cells in ALL including the CAR T-cells against CD22, sequential administration of CAR CD19 and CD22, bispecific CAR for CD19 and CD22, allogeneic CAR, and the other new approaches for the challenges that we still have in CAR T-cells. And those are mainly the CD19 negative relapse. This is up to 40% of the relapses after CAR-T cells and for the persistence of CAR T-cells and toxicity, of course.

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