Successful mobilization of peripheral blood stem cells (PBSCs) with AMD3100 in patients failing to collect with hematopoietic growth factors (HGF) and/or chemotherapy

Abstract

6643 Background: Poor mobilization of PBSCs compromises the application of effective high-dose treatment (HDT) in multiple myeloma (MM). AMD3100, a reversible inhibitor of the binding of SDF-1α to CXCR4, may allow the collection of adequate PBSCs to support HDT in poor mobilizers. Methods: Ten MM pts (3 men, 7 women) with a median age of 60 (range: 52–70) years who had failed to mobilize ≥ 5 million CD34 cells/kg PBSCs, received a daily dose of AMD3100 (240 μg/Kg) approximately 10 hours prior to each apheresis, for up to 7 days. G-CSF (10 μg/Kg) was administered x 4 days prior to and concurrently with AMD3100 until completion of apheresis. Eight pts had <12 months of preceding conventional chemotherapy, and one received HDTx2 > 4 years earlier. Prior to AMD3100 administration, 14 attempts to collect PBSCs were performed following chemotherapy and HGF (n: 11) or HGF alone (n: 3) with a median of 0.19x106 CD34+/Kg (range: 0–2.94x106) collected per attempt. Only one patient had collected a >5x106 CD34+/Kg. All but 3 patients had normal platelet counts at the start of this trial. Results: All patients were leukapheresed for a median of 7 days (range: 3–7) and collected a median number of 2.55x106 CD34+/Kg (range: 0.74–8.04x106). An increase in absolute CD34 cells /μL was observed from a median of 1.6 (0.8 –4.5) prior to AMD3100 to 5.8 (2.3–29.7) 11 hours after the first dose of AMD3100 prior to the first PBSC collection. No grade IV non-hematologic toxicities were seen during mobilization. Four patients collected >5x106 CD34+/Kg, while a meaningful (>2.5x106/kg) number of CD34+ cells was achieved in 6 patients. In none of the AMD3100 collections were myeloma cells identified as measured by cIg/DNA flow cytometry (sensitivity<1%). HDT with AMD3100-collected PBSCs was administered to 1 patient. She achieved ANC>1000/μL on day +12. Conclusions: Clinically meaningful collections of PBSCs can be achieved with minimal toxicity in poor mobilizers after AMD3100 administration. However, poor mobilization with chemotherapy and/or HGF also appears to predict for poor, although seemingly better, collection with AMD3100. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AnorMED, Inc. AnorMED, Inc. AnorMED, Inc.