Biosimilar granulocyte–colony‐stimulating factor for healthy donor stem cell mobilization: need we be afraid?

Biosimilars are approved biologics with comparable quality, safety, and efficacy to a reference product. Unlike generics, which are chemically manufactured copies of small‐molecule drugs with relatively simple chemical structures, the biosimilar designation is applied to drugs that are produced by living organisms, implying much more difficult to control manufacturing and purification procedures. To account for these complexities, the European Medicines Agency (EMA), the US Food and Drug Administration, the Australian Therapeutic Goods Administration, and other regulatory authorities have devised and implemented specific, markedly more demanding pathways for the evaluation and approval of biosimilars. To date, several biosimilars have been approved, including versions of somatropin, erythropoietin, and granulocyte–colony‐stimulating factor (G‐CSF), and several biosimilar monoclonal antibodies are currently in development. The reference G‐CSF product (Neupogen, Amgen) has been used for many years for prevention and treatment of neutropenia and also for mobilization of peripheral blood stem cells (PBSCs). However, concerns have been raised about the safety and efficacy of biosimilar G‐CSF during PBSC mobilization procedures, especially in healthy donors. This article reviews the available evidence on the use of biosimilar G‐CSF in this setting. Aggregate clinical evidence supports the assessment by the EMA of biosimilar and originator G‐CSF as highly biologically similar, with respect to desired and undesired effects.     

Prediction of engraftment after autologous peripheral blood progenitor cell transplantation: CD34, colony‐forming unit–granulocyte‐macrophage,or both?

BACKGROUND: The rate of hematologic recovery after peripheral blood progenitor cell (PBPC) transplantation is influenced by the dose of progenitor cells. Enumeration of cells that express CD34+ on their surface is the most frequently used method to determine progenitor cell dose. In vitro growth of myeloid progenitor cells (colony-forming unit-granulocyte-macrophage [CFU-GM]) requires more time and resources, but may add predictive information. STUDY DESIGN AND METHODS: A series of 323 patients, who underwent autologous PBPC transplantation for multiple myeloma, malignant lymphoma, or locally advanced breast cancer, were studied for the effect of CD34+ dose and CFU-GM dose on hematologic recovery. Measures for engraftment were days to absolute granulocyte and platelet (PLT) counts to greater than 500 per muL and than 20 x 10(9) per L, respectively, and number of PLT transfusions and red cell units required. RESULTS: The CD34+ dose had a median of 8.4 x 10(6) per kg, and the CFU-GM dose a median of 84.9 x 10(4) per kg. The CD34+ and CFU-GM doses showed significant correlation (R = 0.63; p < 0.0001) but a wide variation in the ratio of CD34+ and CFU-GM. Both CD34+ and CFU-GM doses had significant correlation with the measures of engraftment, but for all measures the relationship of CD34+ was stronger. Multivariate analysis and subgroup analysis of patients receiving CD34+ doses of less than 5 x 10(6) per kg also did not reveal an independent predictive value for CFU-GM. CONCLUSION: For prediction of hematologic recovery after autologous PBPC transplantation, determination of CFU-GM dose does not add to the predictive value of the CD34+ dose.