EHA 2019 | CAR-T in hematology with Prof. Mohty: targets, toxicity, resistance & future

CAR T-cells continue to be the major breakthrough in hematology. I think every week, every day, every month we hear something new. Obviously, this is a true revolution which is ongoing. Today, I think, the most popular CAR T-cells are the CD19 directed CAR T-cells, especially in Acute Lymphoblastic Leukemia and

CAR T-cells continue to be the major breakthrough in hematology. I think every week, every day, every month we hear something new. Obviously, this is a true revolution which is ongoing. Today, I think, the most popular CAR T-cells are the CD19 directed CAR T-cells, especially in Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma. During this EHA 2019 meeting, actually, we have mainly educational sessions, going again and again into the data that have been generated over the last couple of years. And definitely, we do have mature data suggesting that a significant proportion of ALL and Non-Hodgkin Lymphoma patients are going to be cured thanks to these CAR T-cells. In terms of safety, what we already know that it looks like we are definitely improving in the management and anticipation, I would say, of the cytokine release syndrome and neurotoxicity. More and more we’re moving towards preventive approaches with the solution map.

Obviously now the big debate is about the mechanism of resistance. One of them is loss of CD19, but there are other different mechanisms of resistance that are being discussed. And, obviously, this is not the end of the story because we need to continue working on this and other antigens that are being investigated, including dual CAR T-cells like combining CD19 and CD22. So this is the story of the CD19 CAR T-cells.

The other major advance that we are seeing, and probably this is going to be the next approval in this field, is the CAR T-cells directed against BCMA in Multiple Myeloma. Data are very convincing, allowing for an extended progression free survival in heavily pretreated patients, including improved survival in those patients who are able to MRD in negativity. The difference when it comes to CAR T-cells in Myeloma versus Lymphoma or ALL is that, unfortunately, it is unlikely that we will be curing Multiple Myeloma patients with CAR T-cells. And this is a reason why I would consider this really as work in progress. Obviously this is a new attractive tool, but we have to refine the use of CAR T-cells in Myeloma, looking into the positioning in the treatment landscape, the sequence. But also trying to armor maybe, these CAR T-cells to try to modify the immune microenvironment.

So in summary, CAR T-cells are really making their way into routine practice. The commercially available products are already giving great results, and many other products are on their way.