Plerixafor for stem cell mobilization in patients with non-Hodgkin's lymphoma and multiple myeloma

Abstract

Objective: To evaluate the literature characterizing the mechanism of action, pharmacokinetics, pharmacodynamics, and therapeutic efficacy of plerixafor for hematopoietic stem cell (HSC) mobilization for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma.

Data sources: A PubMed search (1966-September 2009) was conducted using the key words plerixafor and AMD3100. Manufacturer's prescribing information was also used.

Study selection and data extraction: English-language articles were selected and data were extracted with a focus on clinical studies of HSC mobilization in patients with NHL or multiple myeloma.

Data synthesis: Plerixafor exerts its effect by reversibly blocking the ability of HSC to bind to the bone marrow matrix. When used with granulocyte colony-stimulating factor (G-CSF), plerixafor helps increase the number of HSCs in the peripheral blood, where they can be collected for use in autologous transplantation. In clinical studies, plerixafor was rapidly absorbed after subcutaneous injection, reaching a maximum plasma concentration at approximately 0.5 hours. Plerixafor is renally excreted as the parent drug, with an elimination half-life ranging from 3 to 5 hours. Plerixafor increases circulating CD34+ cells in the peripheral blood, with a peak effect about 6-9 hours after subcutaneous administration. An approximate 2- to 3-fold increase in the CD34+ cell count is seen by the first dose of plerixafor after 4 consecutive days of G-CSF treatment. In 2 Phase 3 studies in patients with NHL or multiple myeloma, addition of plerixafor to G-CSF resulted in a higher CD34+ cell collection with fewer apheresis days, but failed to show better graft durability or overall patient survival for up to 12 months of follow-up.

Conclusions: Clinical trials have demonstrated that the addition of plerixafor to G-CSF was beneficial for HSC mobilization to peripheral blood for collection and subsequent transplantation in patients with NHL or multiple myeloma. Further studies should assess the benefit of the additive use of plerixafor on clinical outcomes.