Results of a Phase 2 Clinical Trial Testing the Efficacy of Plerixafor in Combination with Chemotherapy in the Mobilization of Autologous Blood Hematopoietic Progenitor Cells

Background: The use of plerixafor for mobilization following chemotherapy has not been extensively studied. We tested the hypothesis that adding plerixafor to G-CSF after chemotherapy would increase the proportion of patients mobilizing the target number of hematopoietic progenitor cells in one day to 75% from a historical value of 50%.

Methods: Multiple myeloma (MM) or lymphoma patients for whom autologous stem cell transplantation was intended were eligible. Patients were mobilized with chemotherapy consisting of either cyclophosphamide (N=16), DCEP (N=1), R-ICE (N=10), CHOP (N=2) or R-HyperCVAD (N=5) with daily administration of G-CSF at a dose of 10 mcg/kg/day starting one day after the completion of chemotherapy. The per-protocol plan was subcutaneous injection of 240 mcg/kg plerixafor on the first day on which the neutrophil count was > 1500 cells/uL followed by apheresis the next day. G-CSF, plerixafor and apheresis were repeated daily until 5 (lymphoma) or 10 x 10E6 CD34+ cells/kg (myeloma) were collected.

Results: 17 MM and 28 lymphoma patients with a median age of 57 (range 33-73) were enrolled. 33/45 subjects (76%) collected the target number of CD34+ cells in one day. 12 subjects (7 MM and 5 lymphoma) with a median CD34+ count of 201 cells/uL began apheresis without plerixafor on the first day of monitoring and collected a median of 19 x 10E6 CD34+ cells/kg in one day. The remaining 33 patients (10 MM and 23 lymphoma) received plerixafor with median numbers of 30 CD34+ cells/uL, and 4100 neutrophils/uL that increased to 95 CD34+ cells/uL and 24,799 neutrophils/uL the next day. Plerixafor-treated subjects collected a median of 7.8 x 10E6 CD34+ cells/kg; 22 (66%) collected the target number in one day, while 6 (18%), 3 (9%), and 2 (6%) of the plerixafor-treated subjects required 2, 3, or 4 days of apheresis, respectively. Plerixafor was well tolerated, with 29 total AE, and no SAE recorded during mobilization and/or apheresis. Seven grade 3/4 AE were seen, including thrombocytopenia (4), fatigue (1), anemia (1) and hypokalemia (1). 44/45 enrolled subjects underwent high-dose chemotherapy and re-infusion of CD34+ cells. Plerixafor-treated and non-plerixafor treated transplant recipients promptly engrafted with neutrophil and platelets at median of 12 and 16 days, respectively, with stable hematopoiesis noted at 12 months.

Conclusions: Plerixafor administration after chemotherapy for ASC mobilization is feasible and well tolerated. A greater percentage (76%) of enrolled subjects collected more than the target number of cells in one day of apheresis compared with a historical cohort of patients mobilized with G-CSF after chemotherapy (54%; p<0.03). Daily monitoring of blood counts after chemotherapy is needed to appropriately schedule plerixafor administration. One-fourth of chemotherapy-treated patients mobilized an adequate number of CD34+ in one day without plerixafor.