ATLANTAPatients with multiple myeloma are more likely to mobilize sufficient numbers of hematopoietic stem cells (HSCs) when plerixafor (AMD3100) is given with G-CSF (Neupogen) than with G-CSF alone. John F. DiPersio, MD, PhD, of Washington University School of Medicine, presented interim results of a phase III study evaluating this regimen at ASH 2007 (abstract 445).
Plerixafor is a small-molecule competitive antagonist of CXCR4, a receptor that normally binds to the SDF-1 ligand expressed on bone marrow stromal cells and osteoblasts. By inhibiting the interaction between CXCR4 and SDF-1, plerixafor triggers the rapid release of stem cells out of the bone marrow and into the circulating blood (mobilization). This agent works in concert with G-CSF to rapidly expand the pool of available HSCs that can be collected by apheresis for subsequent transplantation.
The multicenter, randomized double-blind, placebo-controlled phase III trial included adults with myeloma who required an autologous HSC transplant and who were in first or second complete or partial remission.
Patients on both arms received G-CSF (10 μg/kg/d) subcutaneously for 4 days. On the evening of day 4 they were given either plerixafor (240 μg/kg) or placebo. Following a morning dose of G-CSF on day 5 and 10 to 11 hours after treatment with study drug, patients underwent apheresis.
This cycle of evening treatment with study drug, morning G-CSF, and apheresis continued for up to four apheresis sessions or until the target cell number (at least 6 106 CD34+ cells/kg) was harvested.
Those patients who were not able to achieve more than 2 106 cells/kg were allowed to receive plerixafor plus G-CSF without unblinding of the study.
Following myeloablative chemotherapy and HSC transplantation, patients were followed for at least 12 months to assess engraftment and survival.