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Preferential expansion of CD8+CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL
- Source :
- Blood Advances; 20220101, Issue: Preprints
- Publication Year :
- 2022
-
Abstract
- T cells expressing CD19-specific chimeric antigen receptors (CD19-CARs) have potent antileukemia activity in pediatric and adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, not all patients achieve a complete response (CR), and a significant percentage relapse after CD19-CAR T-cell therapy due to T-cell intrinsic and/or extrinsic mechanisms. Thus, there is a need to evaluate new CD19-CAR T-cell products in patients to improve efficacy. We developed a Phase 1/2 clinical study to evaluate an institutional autologous CD19-CAR T-cell product in pediatric patients with relapsed/refractory B-ALL. Here we report the outcome of the phase 1 study participants (n=12). Treatment was well tolerated, with low incidence of both cytokine release syndrome (any grade, n=6) and neurotoxicity (any grade, n=3). Nine out of 12 patients (75%) achieved a minimal residual disease-negative CR in the bone marrow. High disease burden (≥40% morphologic blasts) prior to CAR T-cell infusion correlated with increased side effects and lower response rate, but not with CD19-CAR T-cell expansion. Postinfusion, CD8+CAR T cells had a proliferative advantage over CD4+CAR T cells, and at peak expansion had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation had sustained, durable responses. In summary, initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy, while highlighting the impact of pre-infusion disease burden on outcomes. This trial was registered at www.clinicaltrials.govas #NCT03573700.
Details
- Language :
- English
- ISSN :
- 24739529 and 24739537
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Blood Advances
- Publication Type :
- Periodical
- Accession number :
- ejs59502717
- Full Text :
- https://doi.org/10.1182/bloodadvances.2021006293