Fludarabine AUC and outcomes following Axi-cel in aggressive B-NHL

Scordo M, Flynn JR, Gonen M, et al. Identifying an Optimal Fludarabine Exposure for Improved Outcomes After CD19 CAR T Cell Therapy for Aggressive B-NHL. Blood Advances. 2023; (doi: 10.1182/bloodadvances.2023010302).

Adult patients with aggressive B cell non-Hodgkin lymphoma may benefit from an optimal area under the curve (AUC) dose of fludarabine for lymphodepletion before CD19 CAR T-cell therapy, according to data from a multicenter consortium. Researchers used a population pharmacokinetic model to estimate fludarabine exposure as AUC in 199 adults with aggressive B cell non-Hodgkin lymphomas who received axicabtagene ciloleucel (Axi-cel). They assessed the connection between estimated fludarabine AUC and key outcomes to determine an AUC that optimized effectiveness and tolerability, identifying low (<18 mg*h/L), optimal (18-20 mg*h/L), and high (>20 mg*h/L) AUC cohorts. The cumulative incidence of relapse/progression (relapse/POD) at 6 months was 54% in the low AUC group, 28% in the optimal AUC group, and 30% in the high AUC group. The groups' respective 1-year progression-free survival (PFS) rates were 39%, 66%, and 46%, and their overall survival rates were 58%, 77%, and 66%, respectively. The optimal AUC group had the highest PFS and the lowest risk of relapse/POD, when compared with low AUC, with no elevated risk of cytokine release syndrome. There was a higher risk for any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) in the high AUC group. The highest number of nonrelapse-related deaths occurred in the high AUC group, including three deaths from ICANS.

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Tags: Patients, Treatment, Therapy, Cellular therapy, Survival, Transplant, cell therapy, Science, CART, CD19, scientists