1.
Long-acting granulocyte colony-stimulating factor pegfilgrastim (lipegfilgrastim) for stem cell mobilization in multiple myeloma patients undergoing autologous stem cell transplantation
Danylesko, I., Sareli, R., Varda-Bloom, N., Yerushalmi, R., Shem-Tov, N., Magen, H., Shimoni, A., Nagler, A.
International journal of hematology. 2021
Abstract
Autologous stem cell transplantation (ASCT) is a standard of care in newly-diagnosed multiple myeloma (MM) patients. Several studies before the introduction of novel therapies in MM, demonstrated a pegylated G-CSF to be successful in mobilizing peripheral blood stem cells (PBSCs). Lipegfilgrastim is a novel long-acting G-CSF that is produced by the conjugation of a single 20-kDa polyethelene glycol to the natural O-glycosylation site of G-CSF. Twenty-four MM patients were included for PBSCs mobilization with a single SC injection of 6 mg lipegfilgrastim. PBSC collection was started when the CD34(+) count was > 10 × 10(6) cells/L. The target progenitor cells were 6 × 10(6) cells/kg. The median day of apheresis was + 3 (range 2-5) following lipegfilgrastim. Median peripheral blood CD34(+) count pre-mobilization was of 22.65 (range 3.36-105) × 10(6) cells/L. The median number of leukaphaeresis procedures was 2 (range 1-4). The median mobilized CD34(+) cells/kg were 8.26 (range 0.77-12.42). One patient failed to mobilize and two patients mobilized < 6 × 10(6) cells/kg. Toxicity was mild and transient. Twenty-three patients underwent ASCT following high dose melphalan. All patients engrafted. As lipegfilgrastim is administered only once, it is conceivable that it improves both compliance and quality-of-life (NCT02488382).
2.
Biosimilar Filgrastim (Tevagrastim, XMO2) for Allogeneic Hematopoietic Stem Cell Mobilization and Transplantation in Patients with Acute Myelogenous Leukemia/Myelodysplastic Syndromes
Danylesko, I., Sareli, R., Bloom-Varda, N., Yerushalmi, R., Shem-Tov, N., Shimoni, A., Nagler, A.
Biology of Blood & Marrow Transplantation. 2016;22(2):277-83
Abstract
Human recombinant granulocyte colony-stimulating factor (G-CSF), filgrastim (Neupogen; Amgen, Thousand Oaks, CA, USA), has been widely used for the mobilization of CD34(+) hematopoietic stem cells (HSC) from healthy donors. The experience with biosimilar G-CSF agents in this area is limited. We performed a prospective study assessing Tevagrastim (biosimilar filgrastim, XMO2; Teva, Israel) for mobilization of CD34(+) peripheral blood HSC in HLA-matched healthy sibling donors for transplantation in 24 patients with acute myelogenous leukemia (AML) and high-risk myelodysplastic syndromes (MDS) (NCT01542944). Results were compared to a historical control group of sibling donors who received filgrastim for stem cell mobilization for allogeneic stem cell transplantations in patients with AML and MDS. The healthy donors received Tevagrastim or filgrastim in a dose of 10 mug/kg body weight (BW) subcutaneously for 4 days. The target yields of CD34(+) cells was 5 x 10(6) CD34(+) cells/kg BW of the recipient. A median 10.2 x 10(6) (range, 2.52 to 35.4) and 9.35 x 10(6) (range, 3.7 to 30.6) CD34(+) cells per kg BW were collected in the Tevagrastim and filgrastim groups, respectively. All patients promptly engrafted with a median day of absolute neutrophil count (ANC) of >.5 x 10(9)/L and >1 x 10(9)/L of 13 days (range, 10 to 21) and 13.5 days (range, 10 to 22), respectively in the Tevagrastim group and 12 days (range, 10 to 18) and 13 days (range, 10 to 18) in the filgrastim group, respectively. Platelets reached counts of >20 x 10(9)/L and >50 x 10(9)/L within a median of 14 days (range, 11 to 33) and 17 days (range, 12 to 33) in the Tevagrastim group and 13 (range, 10 to 29) and 15 (range, 10 to 32) days in the filgrastim group, respectively. The donors developed only mild and transient side effects, which were not different between the Tevagrastim study group and the filgrastim historical control group. Similarly, the transplantation-related toxicities and outcomes did not differ between the patients who underwent transplantation with Tevagrastim-mobilized grafts and the filgrastim historical controls. In summary, we observed a similar yield of CD34(+) stem cell mobilization in the Tevagrastim study group and the filgrastim historical control group with similar engraftment kinetic, hematopoietic reconstitution, and transplantation outcome. Tevagrastim administration was safe with minimal side effects and toxicity not different than historical controls. The lack of significant differences for all parameters of stem cell collection, engraftment, and safety with the biosimilar XMO2 Tevagrastim demonstrate the "similarity" of the biosimilar and recombinant human G-CSF in this indication. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
3.
Plerixafor (Mozobil): A Stem Cell-Mobilizing Agent for Transplantation in Lymphoma Patients Predicted to Be Poor Mobilizers - A Pilot Study
Danylesko, I., Sareli, R., Varda-Bloom, N., Yerushalmi, R., Shem-Tov, N., Shimoni, A., Nagler, A.
Acta Haematologica. 2016;135(1):29-36
Abstract
Autologous hematopoietic stem cell transplantation is the standard therapy for refractory/relapsed aggressive lymphoma. The initial step of the procedure involves mobilization and collection of hematopoietic stem cells. G-CSF fails to achieve mobilization in 15-25% of lymphoma patients. Plerixafor is a novel CXCR4 antagonist that can promote mobilization. It has been used successfully in patients after the failure of G-CSF. It is reasonable to test whether plerixafor should become the mobilizing agent of choice in patients expected to exhibit difficulties in mobilization. We initiated a study to assess the use of plerixafor as a first-line stem cell mobilizer in 20 elderly or heavily pretreated patients with non-Hodgkin or Hodgkin lymphoma. The minimum defined CD34+ cell dose of >2 x 106 cells/kg was achieved by 90% of the patients, and for 83% of them with one apheresis procedure. The target CD34+ dose of >5 x 106 cells/kg was achieved by 70% of the patients. The median number of circulating CD34+ cells before and after plerixafor was 14.4 and 42.8 cells/mul, respectively. The post-plerixafor adverse events were mild. All patients promptly engrafted after high-dose chemotherapy treatment. We conclude that plerixafor administration is safe and efficient for upfront mobilization in lymphoma patients predicted to be poor mobilizers. Copyright © 2015 S. Karger AG, Basel.
4.
Mobilization of autologous and allogeneic peripheral blood stem cells for transplantation in haematological malignancies using biosimilar G-CSF
Schmitt, M., Hoffmann, J. M., Lorenz, K., Publicover, A., Schmitt, A., Nagler, A.
Vox Sanguinis. 2016;111(2):178-86
Abstract
BACKGROUND AND OBJECTIVES Biosimilars of the granulocyte colony stimulating factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA) for registered indications of the originator G-CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G-CSF. MATERIALS AND METHODS This article is a meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases. All data sets were weighted for the number of patients and parameters and then subjected to statistical meta-analysis employing the Mann-Whitney U-test followed by the Hodges-Lehmann estimator to assess differences between biosimilar and originator G-SCF. RESULTS A total of 1892 individuals, mostly with haematological malignancies but also including 351 healthy donors have been successfully mobilized for autologous or allogeneic stem cell transplantation using biosimilar G-CSF (Zarzio(TM) : 1239 individuals; Ratiograstim(TM) /Tevagrastim(TM) : 653 individuals). A total of 740 patients with multiple myeloma, 491 with non-Hodgkin's lymphoma (NHL), 150 with Hodgkin's lymphoma (HL) and other diseases are included in this meta-analysis, as well as 161 siblings and 190 volunteer unrelated donors. For biosimilar and originator G-CSF, bioequivalence was observed for the yield of CD34+ stem cells as well as for the engraftment of the transplants. CONCLUSION Biosimilar G-CSF has equivalent effects and safety as originator G-CSF. Copyright © 2016 International Society of Blood Transfusion.