The Comparison of the Biosimilar Filgrastim (Tevagrastim) and the Original Filgrastim (Neupogen) in the Autologous Hematopoetic Stem Cell Mobilization: A Single Center Experience

Abstract

Objective : Autologous hematopoietic stem cell transplantation is a significant treatment modality for several hematological malignancies and some solid tumors. A sufficient dose of CD34+ stem cell mobilization is a prerequisite for successful autologous hematopoietic stem cell transplantation. Granulocyte colony stimulating factor (G-CSF) is usually used alone or in combination with chemotherapy for mobilization. Two types of G-CSF are used in peripheral blood stem cell mobilization; filgrastim (original or biosimilar) and lenograstim. It was aimed to compare the original filgrastim (Neupogen) with the biosimilar filgrastim (Tevagrastimin) in terms of effectiveness in peripheral blood stem cell mobilization. Materials and Methods: Ninety-five patients who underwent stem cell mobilization between January 2015 and November 2018 in the Bone Marrow Transplant Service of Ankara Numune Training and Research Hospital were analyzed retrospectively. We used Cyclophosphamide (low dose: 2g/m or high dose: 3-4 g/m), as a mobilization regimen, on the first day and G-CSF (Neupogen or Tevagrastim) at a dose of 5 g/kg was started one day after chemotherapy, as a mobilization regimen in all patients. Results: Thirty-nine patients were female and 56 were male. The mean age was 51.24±12.38 years. Sixty-four (67.4%) patients had Multiple Myeloma (MM), 20 (21.1%) patients had non-Hodgkin lymphoma (NHL), and 11 (11.6%) patients had Hodgkin lymphoma (HL). Stem cell mobilization was performed with Neupogen in 50 of ninety-five patients and with Tevagrastim in 45 of them. While there was no statistically significant difference between the demographic characteristics of the patients in terms of age, diagnosis, and whether they received radiotherapy or not (p> 0.05); There was a significant difference in terms of the dose of cyclophosphamide (higher dose cyclophosphamide was used more in the arm receiving Neupogen) and gender (gender distribution in the Neupogen arm was equal, there were more male patients in the Tevagrastim arm) (p<0.05). No statistically significant difference was found between the use of original and biosimilar products in terms of achieving the target of 2x10/kg, which is the minimum CD34 cell dose required for adequate engraftment, and 4x10/kg for double transplantation (p>0.05). However, if the target level of CD34 stem cell was above 6x10/kg, a statistically significant difference was observed in favor of Neupogen compared to the Tevagrastim arm (p=0.021). When the neutrophil engraftment days after autologous stem cell transplantation were compared, it was observed that the neutrophil engraftment was shorter in the Neupogen arm compared to the Tevagrastim arm (approximately 1 day) (p=0.015), while the platelet engraftment was similar in the Neupogen and Tevagrastim arms (p=0.186). Conclusion: While the original and biosimilar filgrastim CD34 cell dose show similar efficacy in reaching the target of 2x10/kg for transplantation and 4x10/kg for double transplantation. The difference was observed in favor of the Neupogen arm, when stem cell collection was aimed at above 6x10/kg. The reason for this difference was thought to be related to the higher dose of cyclophosphamide used in the original molecule (Neupogen) arm. We need further studies that were included more cases which are used high-dose cyclophosphamide for comparing the biosimilar molecule (Tevagrastim) with the original molecule (Neupogen).