Biosimilar G-CSF Based Mobilization Of Peripheral Blood Hematopoietic Stem Cells For Autologous and Allogeneic Stem Cell Transplantation

Hematopoietic growth factors including G-CSF are manufactured by the use of recombinant technology. When biologically equivalent agents are manufactured they are termed “biosimilars”. The use of biosimilars in general and in particular for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. The use of biosimilar G-CSF (Ratiograstim^®, Tevagrastim^®, Biograstim^®, Zarzio^®, Nivestim^®) was approved by the European Medicines Agency (EMA) for all the registered indications of the originator (Neupogen^®) including mobilization of stem cells.

We performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization with a biosimilar G-CSF for autologous and allogeneic stem cell transplantation, evaluating mobilization yield and safety profile as well as engraftment and transplantation outcome.

An extensive literature review produced 903 patients mostly with hematological malignancies as well as healthy donors that underwent successful autologous or allogeneic stem cell mobilization respectively using a biosimilar G-CSF (Ratiograstim®/Tevagrastim® or Zarzio®). A total of 519 patients or donors underwent stem cell mobilization with Ratiograstim®/Tevagrastim®, while 384 patients or donors underwent stem cell mobilization with Zarzio®. The indication for stem cell mobilization in hematology patients included 326 with multiple myeloma, 273 with Non-Hodgkin’s lymphoma (NHL), 79 with Hodgkin’s lymphoma (HL), and others. 155 sibling or volunteer unrelated donors were mobilized using either Ratiograstim®/Tevagrastim® or Zarzio®. Biosimilar G-CSF based stem cell mobilization for both autologous and allogeneic transplantation resulted in good mobilization of CD34+ stem cells with side effects similar to reference G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator filgrastim (Neupogen^®) in historical controls. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. (More detailed results regarding yield, engraftment and side effects will be disclosed in the conference.)

In summary, we present the published experience for the use of biosimilar G-CSFs in more than 900 patients and normal family related and volunteer unrelated donors. Both the toxicity profile PBSC yield and efficacy seem equivalent to historical data with the reference G-CSF. Until results from multi-center randomized clinical trials that directly compare biosimilar G-CSF with the originator G-CSF are reported, it is important to collect and summarize all of the available clinical experience in order to allow the transplant community to make informed decisions regarding the choice of G-CSF.

Schmitt:AMGEN: Honoraria; Teva: Consultancy, Honoraria, Research Funding, Travel Grant, Research Grants Other. Publicover:Teva: Travel Grants, unrestricted educational grant Other. Orchard:Teva: Honoraria, Travel Grants, research grants Other. Schmitt:TEVA: Travel grant Other. Nagler:Teva: Honoraria, Travel grants, research grants Other.