Background: AMD3100 potentiates the effect of G-CSF (Filgrastim) to mobilize hematopoietic PBPCs from the bone marrow into peripheral blood (PB) and may decrease the number of aphereses required to collect sufficient PBPCs for transplantation.

Methods: Mobilization treatment consisted of subcutaneous G-CSF 10 ug/kg given in the morning on 5 consecutive days and a single dose of AMD3100 240 ug/kg in the evening of day 4, 10 – 11 hours prior to leukapheresis. These doses of G-CSF and AMD3100 were continued for up to 4 additional days in order to reach the target of ≥ 5 × 10^6 CD34+ cells/kg. Blood samples for FACS analysis of CD34+ cells were obtained immediately prior to dosing with AMD3100 and pre-apheresis the next morning. PK parameters were determined from samples obtained immediately prior to dosing, 0.25, 0.5, 1, 2, 4, 6 and 8 hours after the injection of AMD3100, and just prior to apheresis.

Clinical Results: Nineteen pts have thus far been enrolled, 11 MM and 8 relapsed NHL. AMD3100 was well tolerated. Mobilization characteristics are summarized in table 1; 100% of MM pts and 63% of NHL pts reached the target of 5 × 10^6 CD34+ cells/kg; all collected > 2 ×10^6 CD34+ cells/kg. For apheresis day 1, AMD3100 increased absolute CD34+ counts ≥ 2-fold in 100% of pts; the median increase for MM pts was 3-fold (range: 2–7.7 fold) or an absolute increase of 108 CD34+ cells/uL (range: 40–166), whereas the median increase for NHL pts was 2.7-fold (range: 2.2–3.7 fold) or an absolute increase of 35.5 CD34+ cells/uL (range: 11–99). Among the relapsed NHL pts, who were characterized by lower pre-AMD3100 CD34+ counts, 4 had increase in PB CD34+ cells/ul from < 20 to > 20 and one other increased from 6 to 17. Of the 17 pts who have subsequently been transplanted; median time to engraftment of neutrophils >0.5 ×10^9/L and platelets >20 ×10^9/L was 11 and 18 days, respectively.

PK Results: PK determinations for AMD3100 were completed in a subset of patients (4 MM; 3 NHL) using plasma samples obtained after the first dose. AMD3100 was rapidly absorbed following subcutaneous injection with a median tmax of 30 (range, 15–60) minutes and Cmax of 0.84 (range, 0.77–1.03) ug/ml. Plasma concentrations declined in a bi-exponential manner, with a median elimination half-life of 4.6 (range, 2.71–5.32) hours. The median AUC 0-infinity was 4410 (range, 2682–5165) ug-hr/ml. AMD3100 pharmacokinetics were consistent with results previously obtained in studies conducted using healthy volunteers in the absence of G-CSF.

Conclusions:

  1. AMD3100 was generally safe and well tolerated in both groups.

  2. PK in the cancer patients was similar to that in previously studied healthy volunteers.

  3. AMD3100 increased PBPC mobilization following 4 days of G-CSF, and resulted in collecting large numbers of PBPCs in MM patients and facilitated adequate PBPC collections for poor mobilizers within the relapsed NHL group.

Table 1:

Mobilization characteristics

No. of ptsNo. apheresis days (range)Median CD34+ cells collected (×10^6/kg)>2×10^6/kg collected on day 1>5×10^6/kg collected on day 1
MM 11 1 (1–2) 13.1 (5.8–19.7) 100% 82% 
NHL 8 2 (1–5) 5.6 (2.8–10.6) 88% 50% 
All 19 1 (1–5) 9.0 (2.8–19.7) 95% 68% 
No. of ptsNo. apheresis days (range)Median CD34+ cells collected (×10^6/kg)>2×10^6/kg collected on day 1>5×10^6/kg collected on day 1
MM 11 1 (1–2) 13.1 (5.8–19.7) 100% 82% 
NHL 8 2 (1–5) 5.6 (2.8–10.6) 88% 50% 
All 19 1 (1–5) 9.0 (2.8–19.7) 95% 68% 
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Topics:
engraftment, granulocyte colony-stimulating factor, lymphoma, non-hodgkin, multiple myeloma, pharmacokinetics, plerixafor, recombinant granulocyte colony stimulating factor, stem cells, brachial plexus neuritis, apheresis

Disclosures: R. McFarland, K. Badel, and G. Calandra are employees of AnorMED.; R. McFarland, K. Badel, and G. Calandra have ownership interests (AnorMED).

Author notes

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Corresponding author

2006, The American Society of Hematology
2006
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