Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors

Abstract

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 μg/kg for lenograstim, 9.8 μg/kg for biosimilar filgrastim, and 9.3 μg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF.

Efficacy of three filgrastim‐intended copies for hematopoietic stem cell mobilization in healthy adult and pediatric donors in Mexico

“…On the other hand, the use of biosimilar G‐CSFs for stem cell mobilization in healthy donors was initially met with less enthusiasm although evidence on their safety and efficacy is accumulating . Results from a large retrospective study reported similar findings to ours using the biosimilar G‐CSF Zarzio (Sandoz, Germany) in n = 85 donors compared with patients who received Neupogen and lenograstim, without observing a difference in the number of CD34+ cells collected in the first apheresis session and a 93% first‐apheresis success rate, similar to patients who received the originator and superior to lenograstim . The largest prospective study reported to date in healthy donor mobilization was performed using the Sandoz brand and reported a 91% success rate in one apheresis and demonstrated its safety .…”

Extrapolation in Practice: Lessons from 10 Years with Biosimilar Filgrastim

“…Prospective study of biosimilar filgrastim ( n = 85) vs. lenograstim ( n = 121) and ref filgrastim ( n = 107) for allogeneic SCM [48]…”

Challenge to Predict Mobilized Peripheral Blood Stem Cells on the Fourth Day of Granulocyte Colony-Stimulating Factor Treatment in Healthy Donors: Predictive Value of Basal CD34+ Cell and Platelet Counts

“…Filgrastim and lenograstim are growth factors of choice for mobilizing PBSCs in HDs [9]. Recent evidence supports the safety and efficacy of G-CSF biosimilars for PBSC mobilization in the AlloSCT setting [10,11]. The recommended G-CSF dose is 10 mg/kg/body weight (BW) daily [12], by subcutaneous injection, in daily or twice-daily dosing [13].…”