Plerixafor and G-CSF Versus Placebo and G-CSF in Moderately Mobilizing Patients With Multiple Myeloma to Optimize Hematopoietic Stem Cell Collection Results (OPTIMIZE)

Efficient collection of hematopoietic progenitor cells (HPCs) is essential for autologous stem cell transplantation (ASCT) in multiple myeloma (MM). Although plerixafor is routinely used in poor mobilizers, its role in patients with intermediate mobilization capacity remains unclear. In this randomized, double-blind, placebo-controlled phase IV trial, MM patients with peripheral blood (PB) CD34⁺ counts of 15-40 cells/μL after steady-state G-CSF mobilization were randomized to receive plerixafor or placebo. The primary endpoint was successful collection of ≥ 6.0 × 10⁶ CD34⁺ cells/kg, sufficient for two ASCTs, during a single apheresis session. Secondary endpoints included CD34⁺ kinetics, graft composition, colony-forming capacity, engraftment, immune reconstitution, and safety. Twenty-one patients were enrolled before premature study termination due to changes in first-line MM therapy and the COVID-19 pandemic. Plerixafor significantly increased PB CD34⁺ cell counts compared with placebo (p < 0.001). All patients receiving plerixafor achieved the primary endpoint, whereas none in the placebo group achieved it (p < 0.001). Mean CD34⁺ yield was significantly higher with plerixafor (10.4 ± 1.9 × 10⁶/kg vs. 2.9 ± 1.3 × 10⁶/kg; p < 0.001). Plerixafor-mobilized grafts contained significantly higher numbers of primitive hematopoietic progenitor subsets and demonstrated increased CFU-GM formation, indicating enhanced clonogenic potential. Despite marked differences in graft quantity and quality, engraftment kinetics, graft sustainability, and immune reconstitution were comparable between groups. In MM patients with intermediate mobilization capacity, the addition of plerixafor markedly improved stem cell mobilization efficiency and enriched grafts with functionally robust progenitor cells. These findings suggest that selected patients beyond conventional poor mobilizers may benefit from plerixafor-assisted mobilization. Trial Registration: EudraCT nr.: 2016-004122-41.