作者: B. E. Shaw , D. L. Confer , W. Y. Hwang , D. H. Pamphilon , M. A. Pulsipher
DOI: 10.3324/HAEMATOL.2011.045740
关键词: Lenograstim 、 Intensive care medicine 、 Granulocyte colony-stimulating factor 、 Filgrastim 、 Biosimilar 、 Donation 、 Hematopoietic Stem Cell Mobilization 、 Transplantation 、 Immunology 、 Medicine 、 European union
摘要: The World Health Organization (WHO) defines biosimilars or Similar Biotherapeutic Products (SBPs) as “a biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference (RBP)”.1 As the patents for several RBP have recently expired, there has been a surge interest developing SBP broaden access these drugs through increased global availability reduced cost. However, manufacturing processes remain proprietary and, therefore, are manufactured using separately developed similarly processes. Thus, despite demonstration primary licensing indications, may be differences their ultimate clinical efficacy, adverse event profile immunogenicity. Because possible differences, late-effects also vary. Two ‘branded’ versions (RBP) recombinant G-CSF available internationally: Granocyte (lenograstim, Chugai, Tokyo, Japan) Neupogen (filgrastim, Amgen, Vienna, Austria). Their indications include: reducing duration post-chemotherapy (or transplant) neutropenia, congenital cyclical neutropenia associated with HIV, mobilization peripheral blood stem cells (PBSC) transplantation patients healthy donors; but differ according national regulations. Both agents HSC normal donors European Union (EU). Although (but not lenograstim) routinely used donor USA, this one insert view this, US Food Drug Administration (FDA) continues require close study oversight long-term safety. Prior G-CSF, could only donate bone marrow. Trials investigating use related began early 1990s, followed by data collection unrelated (UD) beginning 1999. Over last ten years marked shift from donation marrow PBSC, due largely preference. In 2010, 9,248 donated mobilized PBSC (WMDA annual report, http://www.worldmarrow.org/). some countries (e.g. UK) introduction UD was delayed registries ethical considerations around drug individuals results no physical benefit them. Indeed, allowed UDs PBSC. Marrow Donor Association (WMDA) international organization fosters collaboration facilitate exchange high quality promote interests (http://www.world-marrow.org/). WMDA maintains database serious events affecting cell products they all accredited expected report to. This approach necessary capture rare splenic rupture, anaphylaxis) recognize trends, it likely that very large numbers need followed-up prolonged periods low incidence events. Additional information on Group Blood Transplantation (EBMT) such German (ZKRD/DKMS) National Program (NMDP) published follow-up outcomes.2–4 Two publications mid-90s5,6 raised concerns about potential short course induce chromosomal damage then predispose development malignancies. experts field produced guidance at time indicate insufficient evidence risk malignancy given not, recommended halt GCSF-mobilized UD.7–10 Two registry based laboratory studies currently being performed investigate claims further. Thus far shown increase abnormalities compared non-donor controls (D Confer E Nacheva, personal communications, 2011). It unknown whether costly can extrapolated biosimilars. Recently, number biosimilar become many countries. Based cost considerations, pressure brought bear health care professionals (HCP) prescribe place originator agent (RBP). While considered reasonable do so settings, HCP caring follow up minimal setting. 2008, EBMT sent letter its centers stating should (related unrelated). position supported WMDA. The aim paper review basis regulatory approval agents, including data, indication make recommendations these. intention entire other comprehensive reviews available.11