EBMT 2022 | CAR-T therapy in pediatric and adult ALL
Arnon Nagler, MD, Chaim Sheba Medical Center, Tel-Aviv, Israel talks on the current status of chimeric antigen receptor T-cell (CAR-T) therapy in acute lymphoblastic leukemia (ALL). Prior to the introduction of CAR-T therapy in pediatric ALL, patients had dismal outcomes. The approval of the CD19-directed CAR-T therapy tisagenlecleucel (tisa-cel) has dramatically improved survival outcomes in relapsed/refractory (R/R) patients. This therapy was later approved in adult patients with R/R ALL based on the results of the ZUMA-3 study (NCT02614066). Prof. Nagler mentions other promising CAR-Ts in development, including CD22 CAR-Ts and bispecific CAR-Ts, and further comments on the role of CAR-T in the ALL treatment regimen. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.
Transcript (edited for clarity)
So I mean, CAR-T really is the very hot topic in all lymphatic malignancies. We started with CD19 CAR-T therapy. It’s a very effective CAR-T with limited off-target effects and is very efficient. And it was started in pediatric ALL by the product of tisa-cells that was approved only up to the age of 25 with very good results in patients with relapsed or refractory ALL and before CAR-T this was an unmet need and had very bad results with survival of 20%, or something like this...
So I mean, CAR-T really is the very hot topic in all lymphatic malignancies. We started with CD19 CAR-T therapy. It’s a very effective CAR-T with limited off-target effects and is very efficient. And it was started in pediatric ALL by the product of tisa-cells that was approved only up to the age of 25 with very good results in patients with relapsed or refractory ALL and before CAR-T this was an unmet need and had very bad results with survival of 20%, or something like this. So with CAR-Ts, you can achieve long-term disease-free survival in ALL less so than in lymphoma, but it’s still extremely beneficial and important in pediatric ALL for the patients that need transplant or celluar therapy.
For adult ALL the ZUMA-3 trial was just published last year showing the benefits of CAR-T in the relapsed or refractory adult ALL, it’s also approved, and now we have a CD19 CAR-T for both pediatric and adult ALL. One of the issues of CAR-T, of course, is the relapse with the CD19. And we now have CAR-Ts, not just against CD19, but also against CD22. These can be given sequentially, or you can give them together. There are also now bispecific CAR-Ts.
So I would say that cellular therapy is extremely important now in the treatment of ALL and you can give it to patients that relapse after transplant, or you can give it before transplant. I’m not sure you can give it instead of transplant. This is again for debate and where to position the monoclonal antibodies blinatumomab and [inaudible] compared to CAR-Ts is again subject for ongoing studies.
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