John Theurer Cancer Center at Hackensack University Medical Center Research Finds Fludarabine Exposure Target Window Tied to Improved Survival for B-NHL
ASH presentation also examines negative effects of Flu over and underexposure common with body-surface areas based dosing prior to CD19 CAR T-Cell therapy
At the ASH annual meeting in December, John Theurer Cancer Center at Hackensack University Medical Center researchers presented CTC registry findings suggest that there is a Fludarabine (Flu) exposure target window associated with improved survival in pts with rel/ref aggressive B-NHL receiving axi-cel. Key findings include:
- Flu underexposure is associated with a higher risk of disease-related treatment failure while overexposure is associated with a higher risk of toxicities.
- Optimal Flu exposure is achievable through personalized, pharmacokinetic-directed dosing.
- Optimized dosing provides a novel, easily modifiable strategy to improve outcomes after CAR T-Cell therapy.
Fludarabine (Flu) is one of the most common lymphodepleting chemotherapy (LDC) agents administered prior to CD19 CAR T cells. The main pharmacokinetic predictors of Flu exposure are weight and glomerular filtration rate (GFR)—not body-surface area (BSA). Standard BSA-dosed Flu leads to highly variable drug exposure across patients.
To test the hypothesis that variable Flu exposure influences outcomes, the researchers estimated Flu exposure and evaluated its association with key outcomes, aiming to identify a target exposure that optimized efficacy and tolerability. These data require further external validation, which is currently underway.
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