Sufficient Mobilization of Peripheral Blood Stem Cells by Single Dose Application of Pegylated G-CSF in Patients with Multiple Myeloma, Interim Analysis of a Phase II Study.

Abstract

Autologous peripheral blood stem cell (PBSC) transplantation leads to significant prolongation of survival in patients with multiple myeloma. For PBSC mobilization a combination of myelosuppressive chemotherapy and granulocyte colony stimulating factor (G-CSF) are administered. The optimal application of G-CSF is twice daily. New G-CSF formulations with prolonged half-life carry the promise of reduced patient strain, increased compliance and via continuously high G-CSF serum levels possibly improved PBSC mobilization. We initiated a study with pegfilgrastim-supported mobilization chemotherapy in stage II and III myeloma patients. Patients received up-front treatment with three cycles of vincristin, doxorubicin, dexamethason (VAD) or thalidomide, doxorubicin, dexamethason (TAD).The mobilization regime consisted of four days chemotherapy with cyclophosphamide 1g/m2 day1, doxorubicin 15mg/m2 day 1-4, dexamethason 40 mg d 1-4 p.o. (CAD) and a single administration of 12 mg pegfilgrastim subcutaneously on day five. To date 17 patients (median age 56, 10 female, 7 male) have received pegfilgrastim and maximum CD34+ cell counts were observed 10-18 days (mean 13 days) after treatment with a range between 24 and 827 (mean: 161) CD34+ cells per μl. 15 patients underwent leukapheresis. In total, 6.6 * 10e6 to 40.5 * 10e6 (mean 15.3 *10e6) CD34+ cells per kilogram body weight were collected. 9 patients achieved the target number of 7.5 * 10e6 CD34+ cells per kilogram body weight during a single apheresis, while 4 patients needed two and 2 patients needed three apheresies on consecutive days. Two patients required additional administration of filgrastim. Two patients received 6 mg pegfilgrastim off study. Both achieved sufficient numbers of CD34+ cells (12.7 and 20.8 * 10e6 CD34+ per kg BW). There were only minimal adverse effects. Four patients reported of bone pain or nausea. Mobilization failures did not occur in this patient population.On the basis of these first results we conclude that a single dose application of 12 mg pegfilgrastim after CAD treatment leads to sufficient mobilization of CD34+ cells in stage II and III myeloma patients comparable to historical data with filgrastim-supported mobilization chemotherapy.