Efficacious and save use of biosimilar filgrastim for hematopoietic progenitor cell chemo‐mobilization with vinorelbine in multiple myeloma patients
Julia‐Tatjana MaulFrank StennerBurkhardt SeifertSarah PfrommerUlf PetrauschMichael K. KießlingUrs SchanzGayathri NairAxel MischoChristian TavernaAdrian SchmidtMario BargetziRoger StuppChristoph RennerPanagiotis Samaras
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Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo‐mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen®). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m 2 intravenously on day 1 and either original filgrastim ( n = 61;58%) or biosimilar filgrastim ( n = 44;42%) at a dose of 5 µg per kg body weight (BW) twice daily subcutaneously starting day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4 × 10 6 HPC/kg BW were collected. All patients proceeded to leukapheresis. In 102 (97%) patients the leukapheresis sessions were started as planned at day 8. The median number of collected HPC was 7.3 × 10 6 /kg BW (0.2–18.3) with original filgrastim compared to 9 × 10 6 /kg BW (4.2‐23.8) with the biosimilar filgrastim ( P = 0.16). HPC collection was successful in 57 (93%) of 61 patients of the original group and in all 44 (100%) patients of the biosimilar group ( P = 0.14). No differences were observed regarding side effects. Duration of neutrophil engraftment after autologous HPC transplantation was similar between the two groups ( P = 0.17). Biosimilar and original filgrastim achieve comparable results in combination with vinorelbine regarding HPC mobilization and transplantation outcome in multiple myeloma patients. J. Clin. Apheresis 32:21–26, 2017. © 2016 Wiley Periodicals, Inc.Keywords:
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Abstract Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%–40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the “rebate trap” with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. Implications for Practice We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing “rebate traps” where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.
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This Viewpoint discusses obstacles that limit the use of biosimilar filgrastim in the United States compared with countries in the European Union and Japan and discusses strategies that might help biosimilar filgrastim use become more widespread.
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Seventy‐seven normal donors underwent leukapheresis for peripheral blood progenitor cell collection beginning on day 4 ( n = 45) or day 5 ( n = 32) of filgrastim mobilization (12 μg/kg/d). The two groups were comparable for age, weight, blood volumes processed during leukapheresis and target CD34 + cell dose to be collected. The day 5 schedule allowed a more consistent achievement of the target cell dose with one apheresis ( P = 0.005) and resulted in the initial collection of a significantly larger number of CD34 + cells ( P = 0.009). There was no statistically significant difference in the leukapheresis yield of lymphoid subsets and natural killer cells.
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Sweet's syndrome has been reported to occur in patients with malignant and inflammatory diseases. It may occur as an adverse reaction to the use of drugs, particularly the recombinant human granulocyte colony-stimulating factor (Filgrastim).
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Eighty‐one first‐time normal donors underwent leukapheresis for peripheral blood progenitor cell (PBPC) collection after mobilization with filgrastim administered either twice‐daily (6 µg/kg every 12 h; n = 40) or once‐daily (12 µg/kg; n = 41) subcutaneously for 3 d. The groups were similar for age, donor blood volume and target CD34 + cell dose to be collected (≥ 4 × 10 6 CD34 + cells/kg recipient). There was no statistically significant difference in the apheresis yield of CD34 + PBPCs (× 10 6 ) per kg recipient weight (5·6 ± 3·3 vs. 5·6 ± 4·3; P = 0·94) and per litre of blood processed (30 ± 17·2 vs. 30·4 ± 19·5; P = 0·92).
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Following the release of the initial presentation of filgrastim (granulocyte colony-stimulating factor), several biosimilars have been developed worldwide.To study the efficacy of a Mexican biosimilar granulocyte colony-stimulating factor in a single transplant center.In a group of 19 consecutive patients with multiple sclerosis given autografts, we employed granulocyte colony-stimulating factors to mobilize stem cells from the bone marrow to the peripheral blood, either the original granulocyte colony-stimulating factor (n = 10) or a Mexican granulocyte colony-stimulating factor biosimilar (n = 9).The efficacy of both agents was similar in mobilization capacity, white blood cell count rise, stem cell collection, and kinetics of auto-engraftment.We conclude that both granulocyte colony-stimulating factor agents were similar in their efficacy to mobilize stem cells and usefulness in autografts.
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BACKGROUND: Information on the safety and efficacy of allogeneic peripheral blood progenitor cell (PBPC) collection in filgrastim‐mobilized normal donors is still limited. STUDY DESIGN AND METHODS: The PBPC donor database from a 42‐month period (12/94‐5/98) was reviewed for apheresis and clinical data related to PBPC donation. Normal PBPC donors received filgrastim (6 μg/kg subcutaneously every 12 hours) for 3 to 4 days and subsequently underwent daily leukapheresis. The target collection was ≥4 × 10 6 CD34+ cells per kg of recipient's body weight. RESULTS: A total of 350 donors were found to be evaluable. Their median age was 41 years (range, 4‐79). Their median preapheresis white cell count was 42.8 × 10 9 per L (range, 18.3‐91.6). Of these donors, 17 (5%) had inadequate peripheral venous access. Leukapheresis could not be completed because of apheresis‐related adverse events in 2 donors (0.5%). Of the 324 donors evaluable for apheresis yield data, 221 (68%) reached the collection target with one leukapheresis. The median CD34+ cell dose collected (first leukapheresis) was 462 × 10 6 (range, 29‐1463). The main adverse events related to filgrastim administration in donors evaluable for toxicity (n = 341) were bone pain (84%), headache (54%), fatigue (31%), and nausea (13%). These events were rated as moderate to severe (grade 2‐3) by 171 (50%) of the donors. In 2 donors (0.5%), they prompted the discontinuation of filgrastim administration. CONCLUSION: PBPC apheresis for allogeneic transplantation is safe and well tolerated. It allows the collection of an “acceptable” PBPC dose in most normal donors with one leukapheresis, with minimal need for invasive procedures.
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Medicare Advantage (MA) and Traditional Medicare face different financing structures and incentives and may implement different strategies to encourage biosimilar uptake. Strategies used by health insurers can influence biosimilar uptake, which can in turn promote savings to insurers and patients.
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