Healthy donor hematopoietic stem cell mobilization with biosimilar granulocyte‐colony‐stimulating factor: safety, efficacy, and graft performance

Abstract

BACKGROUND Biosimilar granulocyte‐colony‐stimulating factors (G‐CSFs) have been available in the European Union since 2008, and Sandoz' biosimilar filgrastim was approved in the United States in March 2015 for all of the reference product's indications except acute radiation syndrome. Biosimilar G‐CSFs have been largely embraced by the medical community, except for some reservations about healthy‐donor stem cell mobilization, for which use outside of clinical studies was cautioned against by some members of the scientific community. STUDY DESIGN AND METHODS In a two‐center safety surveillance study (National Clinical Trial NCT01766934), 245 healthy volunteer stem cell donors were enrolled. Of 244 donors who began mobilization with twice‐daily Sandoz biosimilar filgrastim, 242 received a full (n = 241) or partial (n = 1) course of G‐CSF and underwent apheresis. Efficacy and safety were assessed and are reported here. RESULTS Biosimilar filgrastim was accompanied by the typical G‐CSF class‐related adverse effects of expected frequency and severity. Median mobilization for CD34‐positive stem cells was 97/µL (range, 20‐347/µL); after one apheresis (91%) or two aphereses (9%) from all but three donors (1.2%), cell doses in excess of the typical 4 × 106 CD34‐positive cells/kg of the recipient had been collected (range, 3‐52 × 106/kg). Biochemical and hematologic alterations were consistent with previous reports; all had normalized by the first follow‐up 1 month after mobilization. Stem cell products engrafted with typical probability and kinetics for G‐CSF‐mobilized stem cell products. CONCLUSION These data support the use of biosimilar filgrastim for healthy‐donor stem cell mobilization as safe and effective.

Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio): A Combined Analysis of Phase III Studies

“…This was expected, given the low immunogenic potential of filgrastim, and is in line with previous studies and postmarketing surveillance of biosimilar filgrastim in Europe, where no anti‐rhG‐CSF antibodies have been reported across the clinical program, with more than 3,300 samples tested . Likewise, no safety concerns have been observed in an ongoing safety surveillance study .…”

Comparison of biosimilar filgrastim, originator filgrastim, and lenograstim for autologous stem cell mobilization in patients with multiple myeloma

“…This is in line with the findings of Maul and colleagues 16 as well as Martino and colleagues, 17 who evaluated the CD341 collection results in MM patients after chemomobilization with cyclophosphamide and vinorelbine, respectively, and found comparable mobilization efficacies of the biosimilar filgrastim and reference filgrastim. Recently, Becker and coworkers 24 found the use of biosimilar filgrastim for healthy-donor stem cell mobilization to be safe and effective in a twocenter safety surveillance study (n 5 245). Median mobilization of CD341 cells was 97/mL (range, 20-347/mL); after one (91%) or two apheresis procedures (9%) from all but three donors (1.2%), cell doses exceeding the typical 4 3 10 6 CD341 cells/kg body weight of the recipient could be collected.…”

Factors predicting peripheral blood progenitor cell mobilization in healthy donors in the era of related alternative donors: Experience from a single center

“…Vials of 300 and/or 480 μg were used (filgastrim, Zarzio, Sandoz Pharmaceuticals, or Neupogen, Roche) . The biosimilar filgastrim was incorporated since 2013 . Leukapheresis began on 5th day of G‐CSF treatment.…”

“…Thus, none of the donors included in the study experienced mobilization failure, understood as less than 2 × 10 6 CD34+ cells/kg. Despite CD34+ ×10 6 cells per kg of recipient weight collected were lower in the poor mobilization group (P < 0.001), no differences on engraftment with neutrophils >5.0 × 10 9 /L (16 days (15-18) vs 16 days (14.5-18), P = 0.98) and platelets >20.0 × 10 9 /L (15.5 days (12-29) vs 13 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), P = 0.98) were found in the 148 transplants performed in our institution.…”

“…19 The biosimilar filgastrim was incorporated since 2013. 20 Leukapheresis began on 5th day of G-CSF treatment. Apheresis was performed using a continuous blood cell separator (COBE Spectra until May 2014 and Spectra Optia from June 2014, Terumo BCT) 21 through bilateral peripheral blood venous access (115 donors) or a percutaneous central venous catheter (44 donors).…”