Biosimilar as Effective as Originator G-CSFs in Mobilizing Hematopoietic Stem Cells

Stem cell mobilization is a process used to stimulate the production of hematopoietic stem cells in bone marrow in patients who have received chemotherapy, as well as in unrelated hematopoietic stem cell donors. The standard way to conduct mobilization in hematopoietic stem cell donors relies on using 2 original granulocyte-colony stimulating factors (G-CSFs), filgrastim (Neupogen) and lenograstim (Granocyte). Neither drug has been shown in clinical trials to have an advantage over the other.

Recently, biosimilars of G-CSF have been introduced into stem cell mobilization protocols, but there has been limited experience with biosimilar G-CSF in this area, and the World Marrow Donor Association (WMDA) recommends the use of originator G-CSFs for mobilization in healthy unrelated hematopoietic stem cell donors.

A recent study, by Roiya Farhan and colleagues, published in the September 2017 Annals of Hematology, found that, comparing biosimilar G-CSF (Zarzio) with originator filgrastim and lenograstim in unrelated stem cell donors showed that there was no mobilization failure in any of the 313 donors. The authors conclude that biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as originator G-CSF.

Although the WMDA and the European Society for Blood and Marrow Transplantation both argue against the use of biosimilar G-CSF for the mobilization of stem cells in healthy, unrelated hematopoietic stem cell donors, because of a series of issues with product availability, the study’s authors were able to retrospectively compare the use of the 2 originator G-CSFs, lenograstim (Granocyte) and filgrastim (Neupogen), with the use of biosimilar filgrastim.

Their study was conducted at the Medical University of Warsaw between October 2014 and March 2016. The study’s primary endpoints were the efficiency of CD34+ cell mobilization to circulation and the results of the first apheresis (the collection process by which donor blood is collected via catheter and directed into a cell separator machine where white cells and stem cells are separated from other blood components and collected for use). The authors did not report any serious adverse events in the donors during the study.

There was a small but statistically significant dose difference between lenograstim and filgrastims (mean daily dose was 9.1 µg/kg for lenograstim, 9.8 µg/kg for biosimilar filgrastim, and 9.3 µg/kg for originator filgrastim [P <0.001]). The authors say that this difference could have influenced the final CD34+ cell yield. 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 in cell number 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 1 apheresis in 87% of donors mobilized with lenograstim and in 93% of donors mobilized with the originator and biosimilar filgrastim (P = 0.005).

Mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar among the groups (P = 0.06):

• Lenograstim, 6.2 x 10⁶
• Biosimilar filgrastim, 7.6 x 10⁶
• Originator filgrastim, 7.3 x 10⁶

The authors conclude that there were almost no clinically relevant differences between the drugs, with a similar number of donors needing 1 apheresis in each group. “The results of this study show that biosimilar filgrastim performs almost identically to original products,” the authors conclude. The ongoing prospective study will provide more data and will assess differences in side effects between the drugs.