Plerixafor (Mozobi ^®)Plus G-CSF Is More Effective Than Placebo Plus G-CSF in Mobilizing CD34+ Hematopoietic Stem Cells in Patients with Multiple Myeloma Who Have Low (<20 cells/μl) Peripheral Blood CD34+ Cell Count.

Pre-apheresis peripheral blood (PB) CD34+ cells of < 20 cells/μl is a significant risk factor for poor hematopoietic stem cell (HSC) mobilization and collection in patients with multiple myeloma (MM) undergoing autologous HSC transplantation (auto-HSCT). PB CD34+ cells are routinely monitored to optimize the timing and success of HSC collection after mobilization with cytokines ± chemotherapy. This analysis was designed to compare the efficacy of plerixafor + G-CSF to placebo + G-CSF for mobilization in patients with MM who had pre-apheresis PB CD34+ cell counts < 20 cells/μl. We hypothesized that the addition of plerixafor to G-CSF would improve the stem cell yield in these patients with baseline CD34+ cells < 20 cells/μl.

Data were obtained from a prospective, randomized, double-blind, placebo-controlled, phase 3 clinical trial that compared the safety and efficacy of plerixafor (0.24 mg/kg/day SC) + G-CSF (10 μg/kg/day) to placebo + G-CSF for mobilization and auto-HSCT in patients with MM. PB CD34+ cell count was measured on Day 4, prior to first plerixafor/placebo dose, and on Day 5, 10-11 hours post study treatment. The proportion of patients achieving the minimal (≥2 × 10⁶ CD34+ cells/kg) or optimal (≥6 × 10⁶ CD34+ cells/kg) cell doses in 2 apheresis days, apheresis yields, and time to engraftment were compared between the plerixafor and placebo groups for PB CD34+ cell count <10 cells/μl (PB<10) and <20 cells/μl (PB<20).

In the plerixafor group (n=148), 27 (18%) and 56 (38%) patients had Day 4 PB CD34+ cells/μl <10 and <20 which was as expected identical to the 30 (19%) and 60 (39%) patients in the placebo group, respectively (n=154). Patient characteristics were similar in both groups. Plerixafor + G-CSF resulted in a statistically significant increase in the absolute PB CD34+ cells/ml on Day 5 compared to placebo + G-CSF (p<0.001; Table 1). For patients with PB <10, the median fold increase in PB CD34+ cells in the plerixafor (n = 27) vs. placebo (n = 30) groups was 9.6 vs. 2 (p<0.001). Similarly, for patients with PB <20 the median fold increase in PB CD34+ cells in the plerixafor (n = 56) vs. placebo (n = 60) groups was 6.6 vs. 2 (p<0.001).The median CD34+ cell yield after 2 aphereses was significantly higher in the plerixafor vs. placebo group: 5.44 vs.1.68 × 10⁶ cells/kg (p<0.001; PB<10) and 7.06 vs. 3.27 × 10⁶ cells/kg (p<0.001; PB <20). The proportion of patients achieving ≥2 × 10⁶ CD34+ cells/kg in 2 aphereses was significantly higher in the plerixafor group compared to the placebo group: 92.6% vs. 43.3 % in patients with PB<10 (p<0.001), and 94.6% vs. 66.7% in patients with PB<20 (p<0.001). Similarly, the proportion of patients achieving ≥6 × 10⁶ CD34+ cells/kg in 2 apheresis days was significantly higher in the plerixafor vs. placebo group: 40.7% vs. 3.3 % in patients with PB<10 (p<0.001), and 55.4% vs. 15% in patients with PB<20 (p<0.001). The median time to platelet (19-20 days) and neutrophil (11 days) engraftment was similar in both groups.

These data demonstrate that in patients with MM who are predicted to fail mobilization based on low PB CD34+ cell count, the addition of plerixafor to G-CSF allows for 2-day collection of the minimal and optimal cell dose in a greater proportion of patients compared to G-CSF alone. Thus, addition of plerixafor to G-CSF can decrease the risk of poor mobilization in patients with MM who have PB CD34+ cell counts < 20 or even < 10 cells/μl.

Nademanee:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stadtmauer:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Micallef:Genzyme Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Stiff:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marulkar:Genzyme Corporation: Employment, Equity Ownership. Calandra:Genzyme Corporation: Consultancy, Equity Ownership. DiPersio:Genzyme: Honoraria.