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Updated: Dec 24, 2025
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple
Karen Sweiss1,2, Bhaskar Vemu1, Craig C Hofmeister3
1Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
Aims:
High dose melphalan (HDM) and autologous stem cell transplant (ASCT) is standard of care for multiple myeloma (MM), but there is significant variability in melphalan exposure (area under the plasma drug concentration-time curve, AUC) when using body surface area-based dosing. Our aim was to establish a method of pharmacokinetic (PK) testing for real-time melphalan dose adjustments.
Methods:
We performed a prospective PK study of melphalan 140 or 200 mg/m2 in MM patients undergoing ASCT. Twenty MM patients were administered HDM on days -2 and - 1, with PK sampling at 8-10 time points. PK testing was performed on day -2 in all patients, and on day -1 in 5 patients.
Results:
Less than 20% interpatient variation in the day -2 and - 1 AUC was observed. The day -2 range in AUC (4.95-11.28 mg h/L) confirmed significant interpatient variability. The hypothetical total dose ranged from 133-302 mg/m2 to achieve the total median AUC. A 4-time point AUC (0, 30, 150 and 240 min) highly correlated with the AUC from the 8-time point schedule. A higher AUC correlated with increased risk of febrile neutropenia (P = .05).
Conclusion:
Here we outline the methods to establish novel melphalan dosing using PK testing in MM patients undergoing ASCT to target a desired melphalan AUC.
