Steady State Mobilization of Autologous Blood Stem Cells Using G-CSF and AMD3100 in Patients with Multiple Myeloma (MM).

Background: High dose chemotherapy with autologous stem cell transplantation (ASCT) improves disease free and overall survival in pts with MM; tandem ASCT may further enhance clinical benefits. Mobilization with G-CSF alone fails to yield sufficient CD34+ cells for a tandem ASCT in the majority of MM pts. A mobilization regimen including G-CSF and cyclophosphamide is more effective, but associated with significant toxicity. This phase II study evaluated the efficacy and safety of a non-cytotoxic mobilization regimen of AMD3100 plus G-CSF for ASC mobilization in pts with MM.

Methods: Mobilization treatment consisted of subcutaneous G-CSF (Filgrastim 10 μg/kg) given in the morning on 5 consecutive days and a single dose of AMD3100 (240 μg/kg) in the evening of day 4, 10–11 hours prior to leukapheresis. These procedures could be repeated for up to 5 additional days in order to collect an adequate number of cells for transplantation. Monitoring of CD34+ cells in peripheral blood (PB) was performed immediately prior to each AMD3100 administration and prior to the aphereses. Patients were treated with high dose chemotherapy in preparation for transplantation according to local standard of care guidelines. Pts did not receive hematopoietic growth factors following ASCT. The primary endpoint of the study was safety; secondary endpoints included 1) % of pts with >2-fold increase of CD34+ cells following AMD3100, and 2) % of pts in with hematopoietic recovery between day 14 and day 21.

Results: 31 pts were evaluable, including 19 males (median age: 57 yrs, range: 40–73) and 12 females (median age: 61 yrs, range: 53–67). Pts had received a maximum of 4 prior chemotherapy cycles. The cumulative proportion of pts reaching a target of 5×10^6/kg CD34+ cells was 60% on day 1, 87% on day 2, and 93% on day 3. For the initial mobilization, AMD3100 increased absolute CD34+ counts ≥ 2-fold in 78% of pts (median fold increase: 2.8; range: 1.1–15.2). Additional aphereses showed a ≥ 2-fold increase in 21% of cases (median fold increase: 1.4; range: 0.7–6.5). Overall, the median number of CD34+ cells yielded was 7.1×10^6/kg (range: 3–28×10^6/kg). The majority of pts (n=19) underwent only a single apheresis, whereas additional procedures were needed in 12 cases. Nineteen pts received a single transplant, 11 pts a tandem transplant. Autografts contained a median of 3.1×10^6/kg CD34+ cells (range 2.4–9.2×10^6/kg). After first transplant, median time to neutrophil and platelet engraftment was 14 and 13 days, respectively. All patients had complete engraftment within 20 days except 1 pt who had neutrophil recovery at day 34 (single transplant) and 1 had platelet recovery at day 27 after the 2nd transplant. AMD3100 was well tolerated, drug-related adverse events (AEs) were limited to 2 cases of mild nausea/vomiting.

Conclusions: The addition of AMD3100 to G-CSF doubled the number of mobilized CD34+ cells in the majority of pts, allowing the collection of sufficient CD34+ cells for tandem ASCT in 1–2 aphereses. Unlike chemotherapeutics commonly used to enhance stem cell mobilization, AMD3100 was not associated with any significant toxicity.