Webinar recap
This webinar examined the evidence for model-informed precision dosing of conditioning agents in hematopoietic cell transplantation, then followed one academic health system’s transition from conventional busulfan dosing to Bayesian dosing, a change more than a decade in the making.
Historically, the program set initial busulfan doses by weight or nomogram, then calculated AUC by hand with the linear trapezoidal method, which required six to seven levels per assessment and repeat monitoring on later days. In 2021 it moved busulfan dosing and monitoring to InsightRX, where a population PK model sets the initial dose and Bayesian estimation refines it from as few as three samples.
A retrospective review of pediatric patients with non-malignant disorders compared 44 historically dosed patients with 38 dosed by model. At the first PK assessment, no model-dosed patients fell below 80% of their target AUC, compared with 34% of historical patients. Levels per patient fell from 20 to about 10, saving an estimated $2,500 per patient, and dose adjustments after the second and third doses dropped sharply, from 80% and 68% of patients to 15% and 8%. The data also showed busulfan clearance declining over the four-day course, a reminder that a single early AUC can’t be assumed to hold. Patients with inherited metabolic diseases tended to exceed target, which led the team to develop a model specific to that population.
The session closed with updates to InsightRX’s transplant modules, including a new busulfan model built from more than 9,000 samples across 11 U.S. centers, new modules in development for additional conditioning agents, and a planned multicenter prospective trial of model-based conditioning for children and young adults with inborn errors of immunity.
