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Biol Blood Marrow Transplant. 2009 Jan;15(1):39-46. doi: 10.1016/j.bbmt.2008.10.018.

Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma.

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  • 1Department of Oncology and Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada.


Phase I pharmacokinetic (PK) and pharmacodynamic (PD) studies in healthy volunteers demonstrated that plerixafor (AMD3100), a CXCR4 antagonist, administered either alone or with granulocyte colony-stimulating factor (G-CSF), resulted in dose-dependent mobilization of CD34(+) cells in the peripheral blood. The purpose of this study was to evaluate the safety and the PK and PD of plerixafor with G-CSF in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). This was a phase II, open-label, single-arm study conducted in 2 centers in Canada. Patients aged 18 to 70 years with NHL or MM eligible for autologous transplantation were eligible. A total of 22 patients (8 with NHL and 14 with MM) were enrolled in the study. The patients were given G-CSF (10 microg/kg/day subcutaneously [s.c.]) for 4 days in the morning and plerixafor 240 microg/kg s.c. on the evening before each day of apheresis. Apheresis was initiated 10 to 11 hours after each evening dose of plerixafor and after the morning dose of G-CSF. This regimen was repeated for up to 5 days or until > or = 5 x 10(6) CD34(+) cells/kg were collected. The objectives were to determine the safety and efficacy of plerixafor in patients with NHL and MM, and the PK and PD of a single 240-microg/kg dose of plerixafor administered after 4 days of G-CSF mobilization in these patients. The median absolute peripheral blood CD34(+) cell count increased from 24.0 cells/microL before plerixafor administration to 75.0 cells/microL before the first apheresis (10 to 11 hours after treatment with plerixafor). The median number of CD34(+) cells collected in a median of 1 day was 5.7 x 10(6) cells/kg in the patients with NHL and 12.0 x 10(6) cells/kg in those with MM. All patients underwent transplantation with prompt and durable engraftment. The PK profile of plerixafor was characterized in 13 patients (5 with NHL and 8 with MM). Overall, the PK parameters were comparable in the patients with NHL and those with MM. Plerixafor was rapidly absorbed after s.c. administration with no observable lag time, with peak plasma concentrations occurring 0.5 hour after administration in most patients. Plerixafor was rapidly cleared, with a median terminal half-life of 4.6 hours. The median maximum increase in the number of circulating cells from baseline was 4.2-fold (range, 3.0- to 5.5-fold), with the maximum fold increase occurring approximately 10 hours after plerixafor injection for all patients. The plerixafor PK and PD profiles in the study patients were consistent with those in healthy volunteers and support the current dosing regimen and timing of apheresis. Plerixafor was safe and effective in mobilizing CD34(+) cells for transplantation.

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