EHA 2021 | ZUMA-4: 36 month follow-up of brexucabtagene autoleucel for pediatric/adolescent R/R B-ALL
Daniel W. Lee, MD, University of Virginia, Charlottesville, VA, discusses the long-term results from Phase I of the ZUMA-4 trial (NCT02625480) exploring brexucabtagene autoleucel chimeric antigen receptor T-cell (CAR-T) therapy in pediatric or adolescent patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). 24 children and adolescents have been treated with brexucabtagene autoleucel in the trial so far. Dr Lee discusses 36 month follow-up data, which demonstrated an overall complete remission rate of 75% 64%, and 67% in the 2×10^6, 1×10^6 (68-mL), and 1×10^6 (40-mL) groups, and gives an overview of the safety data. All patients who responded had undetectable measurable residual disease. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
We treated 24 children and adolescents with refractory B-cell leukemia with KTE-X19, and we presented our 36-month median follow-up data at EHA this year. About 25% of our patients had a prior transplant before receiving CAR T-cell therapy and that’s important to know because they’re heavily pretreated patients. Overall, our toxicity rates were very in line with the other CD19 CAR products and were quite manageable...
We treated 24 children and adolescents with refractory B-cell leukemia with KTE-X19, and we presented our 36-month median follow-up data at EHA this year. About 25% of our patients had a prior transplant before receiving CAR T-cell therapy and that’s important to know because they’re heavily pretreated patients. Overall, our toxicity rates were very in line with the other CD19 CAR products and were quite manageable. There were no deaths on the study related to these toxicities and our CR and CRi rate was about 67%, with 75% of all treated patients achieving an MRD negativity.
One question that comes up oftentimes is what do we do after the CAR T-cell and the study here was agnostic and did not dictate the required post-treatment or not. However, 87% of the patients who responded in our study did end up going to a transplant after receiving CAR T-cell therapy.
Importantly, the take home here is that not only is KTE-X19 a safe product for highly relapsed and refractory children and adolescents with leukemia, but the median overall survival at the recommended Phase II dose of 1 million CAR T-cells per kilogram was not reached, with about 87% of the patients alive at 24 months that were treated at the recommended Phase II dose.
So, I think that this data is really exciting and is consistent with a lot of the other CD19 CAR data that is out there. The advantages here, aside from the great long-term follow-up, is that the products were delivered to the patients on an average of 17 days from the time that they were apheresed. So, they were delivered to the site an average of 17 days from the time that they were collected. And that’s really quite rapid and of incredible importance for this patient population with highly refractory disease. So currently the KTE-X19 ZUMA-4 study is enrolling in the Phase II, and we actually have expanded enrollment to include those with Burkitt’s leukemia lymphoma, as well as B-cell non-Hodgkin’s lymphomas.
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Disclosures
Daniel W. Lee, MD, has participated in a consultancy role for Harpoon Therapeutics; has participated in an external advisory board for Amgen and Juno/Celgene/BMS; has received institutional research funding from Kite Pharma/Gilead; and is the spouse of an employee of Karyopharm Therapeutics.
