Efficacy of Administration of Plerixafor (Mozobil®) at 5:00 PM for Stem Cell Mobilization (SCM) in Patients Receiving Autologous Stem Cell Transplant.

In the phase 3 clinical trials of plerixafor plus G-CSF for SCM, plerixafor was administered at 10:00 pm on days prior to apheresis. This dosing schedule is based on the peak level of CD34+ cells in the peripheral blood (PB) at 11-14 hours after administration; however PB CD34+ cell levels were elevated from 4-18 hours after plerixafor administration. Due to inconvenience in dosing plerixafor at 10:00pm, we took advantage of its pharmacodynamic profile and explored an alternative dosing schedule, giving plerixafor at 5:00 pm. Here, we report our initial experience with the efficacy of this schedule.

Between 01/09 & 08/09, 22 candidates for autologous stem cell transplant (13 female; mean age = 59, range 32-69; 9 MM, 11 NHL & 2 HD) received plerixafor plus G-CSF for SCM. Eight (4 female) were previous mobilization failures; 3 had failed G-CSF alone and 5 had failed chemotherapy + G-CSF; 2 had failed >1 mobilization. At the time of mobilization, 6 patients (27%) were in CR and 16 (73%) were in PR. Eight patients (36%) had disease in the bone marrow, 7 of these had MM and 1 had NHL. Of the 9 MM patients 3 (33%) had previous lenalidomide therapy. Nine patients (41%) had received >2 different chemotherapy regimens prior to mobilization; 2 of these had failed traditional mobilization with either G-CSF or chemo + G-CSF. Seven patients (32%) had, had previous radiation therapy, of whom 2 had failed traditional mobilization. Our mobilization protocol for autologous SCM consisted of G-CSF 10mcg/kg given at daily at 6:00 am beginning on day 1 and plerixafor 0.24mg/kg SQ x1 (0.16mg/kg if creatine clearance < 50ml/min) given daily at 5:00 pm in our Outpatient Clinic beginning on day 4. Apheresis began at 8:30 a.m. on the morning of day 5. The minimum collection goal was 2 × 106 CD34+cells/kg per transplant while the maximum goal was 4 × 106CD34+cells/kg per transplant. SCM and apheresis were stopped after 1 collection if the maximum goal was reached or after the minimum goal was reached on any subsequent day.

Administration of G-CSF plus 5:00 pm plerixafor resulted in a median PB CD34+ cell count in the morning of apheresis of 32.1 CD34+ cells/ml (range, 1.2-135.7). The median total apheresis yield was 4.83 × 106 CD34 cells/kg (range, 0.06-10.98 × 10⁶) in a median of 2 days of apheresis (range, 1-4). Of the patients with multiple myeloma, 3/9 (33%) collected >6 × 106 CD34 cells/kg with a median time of 1.3 days, although per our protocol patients were stopped after 2 apheresis sessions if >4 × 106 CD34+ cells/kg had been collected. 2/22 patients (9%) failed a plerixafor mobilization. One of these had MM and had failed 2 previous traditional mobilization attempts; this patient reached the minimum collection goal after a second plerixafor mobilization attempt following a 3-week break. The other had received 4 previous chemotherapy regimens for NHL prior to mobilization. Nineteen patients (86%) had proceeded to transplant as of August 12th 2009, including the patient with a second plerixafor mobilization. The median days to neutrophils and platelet engraftment were 16 (range, 14-26) and 9 (range, 10-14) respectively. The side effect profile was similar to that described previously.

An alternative dosing SCM regimen giving at 5:00 pm allowed >90% of the patients to collect the minimum CD34+cell dose necessary to proceed to transplantation. This dosing schedule is more convenient and ensures 100% compliance with plerixafor dosing.

Tornatta:Genzyme: Consultancy, Speakers Bureau. Off Label Use: Plerxiafor is a chemokine recpeptor antagonist approved for use in pts with MM and NHL for mobilization of stem cells for autologous transplant. Our information includes patients with HD who were mobilized using plerxafor for stem cell mobilization and ultimately autologous stem cell transplantation. Fung:Genzyme: Consultancy, Speakers Bureau.