SOHO 2023 | Novel CAR-T constructs being investigated for the treatment of ALL

CAR-T therapy has obviously revolutionized the field of hematological malignancies, DLBCL, multiple myeloma, and we know CAR-T cell therapies are approved for pediatric ALL, as well as adult ALL. In adult ALL, currently, the only approved product in the United States is a product called brexucabtagene or brexu-cel, which is a CD28-based CAR targeting CD19, and that has been an FDA-approved product for the last couple of years. We are seeing patients being treated in the real-world setting. And what we know from those trials, the clinical trial which let to the approval, is that about 70% of the patients achieve an MRD negative remission after receiving brexu-cel. Those patients, when followed along their remission duration, is upwards of one and a half years. There are other CAR-T constructs which are also coming along. There have been published Phase II data with a company called Autolus- they have a CAR-T called obe-cel, which again has been published recently. That is something we are expecting and waiting for FDA to state what they are going to do with that in terms of the approval strategy. So that is the CD19 CAR-T, but there are other CAR-T constructs: CD19 with CD22 or 19, 20, 22 triple CAR-T together, and also allogeneic CAR-Ts including UCART22 and others which are in clinical trials right now, and I think we will have to see how that pans out in the future. So certainly, I think CAR-Ts are changing how we manage patients with ALL. Currently, they are approved for relapsed/refractory ALL, but there are trials designed for using CAR-T as a consolidation strategy, in MRD positive state, even MRD negative state. Also, eventually, I think that CAR-Ts will move into the frontline setting as a consolidation after you have done one or two rounds of standard chemotherapy for a patient.