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EBMT 2022 | HD-CAR-1: 3rd-generation CD19-directed CAR-Ts for R/R CLL

Patrick Derigs, MD, University Hospital Heidelberg, Heidelberg, Germany, describes the design of the third-generation CD19-directed chimeric antigen receptor T-cells (CAR-Ts) evaluated in the Phase I/II HD-CAR-1 academic study (NCT03676504), and comments on the results of this study in patients with high-risk chronic lymphocytic leukemia (CLL) who have relapsed after chemoimmunotherapy or allogeneic hematopoietic stem cell transplantation (alloHSCT). The T-cells used in this study were transduced with a third-generation retroviral vector containing two costimulatory domains, CD28 and 4-1BB, to increase the efficacy and durability of CAR-Ts. The study reported a rapid CAR-T expansion, with responses in all seven evaluable patients. In addition, the four patients treated with the highest CAR-T dose are in complete remission. Regarding safety, the study reported one case of severe hematotoxicity and no severe cases of cytokine release syndrome (CRS) or neurotoxicity. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.