Background: The addition of AMD3100 to a G-CSF mobilization regimen increases the number of hematopoietic stem and progenitor cells (HSPCs) that can be collected by apheresis, allowing the successful (re)mobilization and transplantation of MM patients. This single-arm, open-label, study was therefore initiated to determine if AMD3100 alone could successfully mobilize HSPCs in MM patients for autologous stem cell transplantation (ASCT). This is the first clinical trial of HSPCs mobilized by AMD3100 alone in the autologous transplant setting.

Methods: Patients received 240 μg/kg AMD3100 followed by apheresis 6 hours later. Dosing and apheresis could be repeated for up to 4 consecutive days or until ge;4 × 106 CD34+ cells/kg were collected. Post-transplant follow-up included daily WBC measurements until leukocyte engraftment (≥0.5 × 109/l for 3 consecutive days or ≥1 × 109/l for 1 day), and platelet engraftment (≥20 × 109/l for 7 days).

Results: Nine patients have been enrolled. The median number of CD34+ cells collected was 2.7 × 106/kg (Range:1.9– 4.6), completed in 4 apheresis days by 8 patients and 3 days by 1 patient. Six patients (67 %) mobilized ≥2 × 106 CD34+ cells/kg and 2 pts (22 %) mobilized ≥4 × 106 CD34+ cells/kg. All patients were transplanted; 1 patient received tandem transplants with study cells; 1 patient received tandem transplants, the first transplant with study cells followed by a second transplant with G-CSF mobilized cells. Median time to PMN engraftment was 10 days (Range: 10–11 days); median time to PLT engraftment was 21 days (Range: 15–33 days, except for 1 patient with platelet recovery some time between day 23 and 82). One patient with Plasma Cell Leukemia died of disease relapse at 6 months. Engraftment was durable with a follow-up of over 19 months in the earliest transplanted patient. AMD3100 was safe and generally well tolerated with the most common adverse events being injection site reactions, GI upset, and paresthesias. There were no drug-related severe adverse events.

Conclusions: AMD3100 alone mobilizes autologous HSPCs that provide prompt and durable engraftment, indicating that AMD3100 mobilizes functional HSPCs independent of the presence of G-CSF. These results are consistent with and reinforced by observations made using AMD3100 to mobilize allogeneic HSPCs [Devine et al., ASH 2005, #299]. While the number of cells mobilized by AMD3100 alone is relatively modest, AMD3100 plus G-CSF mobilizes a more primitive subset of CD34+ cells than G-CSF alone which could potentially translate into fewer CD34+ cells being required for transplantation when AMD3100 is part of the mobilization regimen [Seeger et al., ASH 2005, #1969]. Therefore, further evaluation of dose and schedule, as well as the role of CD34+ phenotype, is required to optimize HSPC mobilization with single-agent AMD3100.

Disclosures: Product is not yet licensed. All discussions are off label.; Karin Badel and Gary Calandra are employees of AnorMED.; Neal Flomenberg has consulted for AnorMED.; Neal Flomenberg - Speakers Bureau.

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