Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Pharmacoeconomic issues in stem cell mobilization.

BACKGROUND: recently, stem cell mobilization has made dramatic progress, that ended up in an increasing number of aphereses at target for autologous peripheral stem cell transplantation (ASCT). The aim of this research is investigating the cost-effectiveness of stem cell mobilization. METHODS: a narrative review of the literature was carried out, searching for primary contributions written in English and published during 2000-2023 on cost-effectiveness analysis (CEA) of stem cell mobilization in patients entitled to ASCT. The PubMed database was searched with the following sets of keywords: cost-effectiveness AND apheresis AND myeloma (PubMed_1); cost-effectiveness AND stem cell mobilization (PubMed_2). Articles included in the analysis were assessed via two different checklists. RESULTS: sixty-six entries were retrieved. Five out of 66 (PubMed_1: 4 out 17; PubMed_2: 1 out of 49), 4 CEAs and 1 cost-utility analysis (CUA) fit the research goal. Four out of 5 contributions proved to be in line with most of the items included in the two assessment grids. However, the most relevant missing features in some of the included contributions were: study perspective, healthcare resources valuation, and sensitivity analyses. DISCUSSION: most of the articles included in this research show that chemotherapy-free stem cell mobilization is cost-effective according to different standpoints. Future health economic research on this topic should establish local threshold values for incremental apheresis at target and explore the heterogeneity of CEA (and CUA) to determine oncohaematological diseases and patient categories for which chemotherapy-free stem cell mobilization is cost-effective in different healthcare systems, given local budget constraints.

Economic evaluation of plerixafor addition in the mobilization and leukapheresis of hematopoietic stem cells for autologous transplantation: a systematic review.

INTRODUCTION: Although plerixafor in association with granulocyte colony-stimulating factor (G-CSF) can improve mobilization and collection of hematopoietic stem cells (HSC) by leukapheresis, cost may limit its clinical application. The present study systematically reviews economic evaluations of plerixafor plus G-CSF usage compared to G-CSF alone and compares different strategies of plerixafor utilization in multiple myeloma and lymphoma patients eligible for autologous HSC transplantation. AREAS COVERED: Relevant economic evaluations, partial or complete, were searched on PubMed, Embase, LILACS, and Cochrane Central Register of Controlled Trials for a period ending 30 June 2021. This systematic review was reported following the PRISMA Statement. Six economic evaluations were included, considering the use of upfront or just-in-time plerixafor compared to G-CSF alone or other plerixafor strategies. Most comparisons showed both increased cost and health benefits with the addition of plerixafor. Most analyses favored just-in-time plerixafor compared to upfront plerixafor, with a probable preference for broader cutoffs for just-in-time plerixafor initiation. EXPERT OPINION: Plerixafor is a potentially cost-effective technology in the mobilization of HSC in patients with multiple myeloma and lymphomas eligible for autologous HSC transplantation. There is a decreased number of leukapheresis sessions and remobilizations and a higher yield of CD34+ cells.

MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.

Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

Plerixafor strategies for autologous hematopoietic cell transplant mobilization: A comparison of efficacy and cost.

Addition of plerixafor (P) to granulocyte colony stimulating factor (G-CSF) during peripheral blood mobilization of hematopoietic stem cells (HSC) increases the number of patients meeting collection goals prior to autologous stem cell transplant (aSCT). However, use of P is not universal among transplant centers due to cost. This study aims to compare clinical and financial impacts of using an algorithm-based P mobilization strategy versus use in all patients. This was a single center, retrospective analysis of adult patients with myeloma or amyloidosis receiving aSCT who received apheresis of their HSC between 3/1/2017 and 3/1/2019. Patients prior to 3/1/2018 were classified as receiving P "per algorithm" and those after this date were classified as "up-front" P. For the per-algorithm group, P was given for a pre-apheresis CD34+ cell count of <20 cells/µL on mobilization day 5 and patients returned on day 6 for apheresis. Of the 129 patients included, 55 received P per-algorithm and 74 received up-front P. There was a reduction in median number of apheresis days (1.5 vs 1 day, p < 0.001) and an increase in median number of CD34+ cells collected (6.6 vs 8.5 × 106 cells/kg, p < 0.001) with up-front P. Up-front P increased drug cost but reduced apheresis costs, which resulted in a net savings of $121 per patient in total mobilization costs. These findings suggest that use of up-front P for mobilization significantly reduces apheresis days and increases HSC collection yield without increasing overall cost per patient.

Multiple Myeloma: Risk Adapted Use of Plerixafor for Stem Cell Mobilization Prior to Autologous Stem Cell Transplantation is Effective and Cost Efficient.

BACKGROUND: We used plerixafor in 'a risk adapted approach' for stem cell mobilization for multiple myeloma (MM) patients prior to autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Between January, 2017 and December, 2019 105 consecutive patients of MM were recruited (Study Cohort). Patients received inj G-CSF 10 µg/kg in 2 divided doses for 5 days. Day 4 peripheral blood (PB) CD34+ count was used as a guide; if count was < 20 cells/µl, patients received plerixafor. For those with ≥ 20 cells/µl apheresis was commenced on day 5. We compared their outcome with 156 MM patients transplanted between 2012 and 2016 with G-CSF mobilized PB stem cells (Control Cohort). Primary end point was to collect ≥2.0  ×  106 CD34+ cells/kg (minimal harvest). Secondary end points were: no of apheresis sessions, percentage of patients with optimal stem cell harvest (≥4.0  ×  106 CD34+ cells/kg) and cost analysis. An intent to treat analysis was done. RESULT: 96.2% of patients achieved ≥ 2.0  ×  106 CD34+ cells/kg in the study cohort vs. 87.2% in the control cohort, P < .01. Mean apheresis sessions were 1.5 vs. 1.7 respectively, P < .014 . Optimal stem cell harvest was 29.5% vs. 16%,P = .23. Days for neutrophil engraftment (P < 0.025) and for IV antibiotics (P < .0017) were favorable for the study cohort. Incremental cost effectiveness ratio was $ 15.80/- and $ 10.56/- per 1% increase to achieve a minimal and optimal harvest. CONCLUSION: Plerixafor in this risk adapted strategy resulted in successful mobilization, decreased time to engraftment and was cost effective.

Impact of a grant program to spur advances in sickle cell disease research.

More than 20 years ago, clinical trials and federal grant support for sickle cell disease (SCD) research were not on par with support for other genetic diseases. Faced with the opportunity to spur research and advance treatments for SCD, and at the recommendation of advisors, the Doris Duke Charitable Foundation (DDCF) offered an SCD research funding opportunity starting in 2009 through its Innovations in Clinical Research Awards (ICRA) program. Twenty-eight new grants of $450 000 for direct costs over 3 years and 7 renewals were awarded, for a total investment of $17 million. Only about half the research teams garnered follow-on funding directly related to their ICRA projects, but the financial return on the research investment was substantial (∼4 times the original $17 million or 300%). All but 1 of the ICRA investigative teams published original research reports that acknowledged DDCF as a source of funding; the median number of publications per team was 3. Major innovations in the diagnosis and treatment of SCD included but were not limited to a demonstration that genetic modification of BCL11A enhancer is a potentially important treatment modality, establishment that plerixafor mobilization is safe and effective for those with SCD, development and validation of a new diagnostic called SCD BioChip, and evidence that hydroxyurea treatment is safe and efficacious in African children. These outcomes show that relatively small research grants can have a substantial return on investment and result in significant advances for a disease such as SCD.

Cost saving, patient centered algorithm for progenitor cell mobilization for autologous hematopoietic cell transplantation.

Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms.

Chemotherapy-based versus chemotherapy-free stem cell mobilization (± plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis.

Given the availability and efficacy of the mobilizing agent plerixafor in augmenting hematopoietic progenitor cell mobilization with granulocyte colony-stimulating factor (G-CSF), there is a strong case for comparing the cost-effectiveness of mobilization with G-CSF + cyclophosphamide versus G-CSF alone. This study investigated the cost and effectiveness (i.e., successful 4 million-CD34+ collection) of G-CSF alone versus high-dose cyclophosphamide (4 g/m2) + G-CSF mobilization (± on-demand plerixafor) in patients with multiple myeloma (MM) eligible for autograft in Italy. A decision tree-supported cost-effectiveness analysis (CEA) model in MM patients was developed from the societal perspective. The CEA model compared G-CSF alone with cyclophosphamide 4 g/m2 + G-CSF (± on-demand plerixafor) and was populated with demographic, healthcare and non-healthcare resource utilization data collected from a questionnaire administered to six Italian oncohematologists. Costs were expressed in Euro (€) 2019. The CEA model showed that G-CSF alone was strongly dominant versus cyclophosphamide + G-CSF ( ± on-demand plerixafor), with incremental savings of €1198.59 and an incremental probability of a successful 4 million-CD34+ apheresis (+0.052). Sensitivity analyses confirmed the robustness of the base-case results. In conclusion, chemotherapy-free mobilization (± on-demand plerixafor) is a "good value for money" option for MM patients eligible for autograft.

Medical database analysis of japanese multiple myeloma patients with planned stem cell transplantation (MEDALIST) - a focus on healthcare resource utilization and cost.

This study explored the burden associated with stem cell mobilization, with or without cyclophosphamide (CPA), in patients who intended to receive autologous stem cell transplantation (ASCT) for multiple myeloma (MM). A Japanese health care claims database (MDV) was used to analyze the health care resource utilization patterns and medical cost between 2013 and 2016 (pre-plerixafor launch). The patients were further categorized into groups who received granulocyte-colony stimulating factor (G-CSF) alone or G-CSF + CPA group and analyzed in both mobilization and ASCT phases of treatment. Overall, there were more MM patients who were treated with G-CSF + CPA combination therapy than G-CSF alone. Length-of-stay was 1.6 times longer in the combination group during the mobilization phase. A reverse trend was observed during the ASCT phase. Direct cost was approximately 1.2 million yen during the mobilization phase and 2.3 million yen during the ASCT phase, with hospitalization basic fee accounting for the highest proportion in both groups and phases. A substantial amount of healthcare resource and cost was consumed in both phases. This study may serve as a basic reference for further health technology assessment of new medicines such as plerixafor. Further investigation of differences between treatment groups is warranted.

Efficacy of a conversion from filgrastim to filgrastim-sndz in stem cell transplant patients undergoing mobilization.

During autologous stem cell transplant, granulocyte colony-stimulating factors (G-CSF) serve the integral role of mobilizing hematopoietic cells into the peripheral blood for subsequent collection by leukapheresis. Filgrastim (Neupogen®) is a G-CSF and affects hematopoietic cells by stimulating growth and differentiation of neutrophils. Filgrastim-sndz (Zarxio®), a biosimilar of filgrastim, received landmark approval as the first biosimilar product approved by the FDA in the United States. As a result of the recent FDA approval, our medical center made the conversion in August 2016 from using filgrastim to filgrastim-sndz to provide patients the same benefits of the filgrastim injection at a reduced cost. This retrospective, observational cohort study evaluated the comparative efficacy of the filgrastim-sndz biosimilar in 147 patients who underwent mobilization prior to stem cell transplant with filgrastim between 1 August 2015 and 31 July 2016 or filgrastim-sndz between 1 September 2016 and 30 November 2017. The mean number of CD34 cells collected during apheresis was 7.38 × 106 in the filgrastim group and 8.86 × 106 in the filgrastim-sndz group. Filgrastim-sndz was significantly non-inferior, as the difference between filgrastim and filgrastim-sndz was -1.48 × 106 with an upper 95% confidence bound equal to -0.24 × 106 that did not include the non-inferiority margin of 1 × 106 (p = 0.0006). The median number of days of apheresis was 2 in both groups (p= 0.3273). In conclusion, the biosimilar product was non-inferior for mobilization and the conversion from filgrastim to filgrastim-sndz afforded patients similar efficacy for mobilization in stem cell transplant at a reduced cost.

[Cost-effectiveness of peripheral blood stem cell collection using plerixafor: a single-center study].

Plerixafor is increasingly used in combination with granulocyte-colony-stimulating factor (G-CSF) for peripheral blood stem cell collection. Although it is an expensive drug, its cost-benefit performance is not well investigated. Thus, we analyzed its cost-effectiveness in our hospital. A retrospective observational analysis was performed in patients who underwent stem cell collection between December 2013 and November 2018. A total of 203 patients were investigated and classified into three groups according to their pre-mobilization regimen: G-CSF alone, G-CSF and cyclophosphamide (G+CY), and G-CSF and plerixafor (G+plerixafor). The cost-effectiveness of apheresis of the collected cluster of differentiation (CD) 34+ cells was assessed based on two viewpoints: cost of drugs and cost of equipment. Due to the high cost of plerixafor, the cost of apheresis was higher in patients who received G+plerixafor. However, the difference narrowed when we calculated the cost to collect 2.0×106 CD34+ cells/kg body weight required for a single transplant. The number of stem cells collected from patients who received G+plerixafor was higher than those who received other regimens (median CD34+ cells harvested/day were 2.90 for G-CSF, 2.13 for G+CY, and 4.63 for G+plerixafor, ×106/kg body weight, P<0.01). Our results show that plerixafor enables efficient apheresis.

Utilization and Cost Implications of Hematopoietic Progenitor Cells Stored for a Future Salvage Autologous Transplantation or Stem Cell Boost in Myeloma Patients.

Autologous hematopoietic cell transplantation (autoHCT) is a standard initial treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient hematopoietic progenitor cells (HPCs) for 2 autoHCTs in all eligible patients. Despite a lack of published data on the utilization of HPCs stored for future use, it is common practice across transplantation programs to collect enough HPCs for 2 autoHCTs in MM patients. In this single-center retrospective study, we analyzed the utilization of HPCs collected and stored at the time of first autoHCT in patients with MM, along with the cost implications of HPC collection targets sufficient for 2 transplantations. In a cohort of 400 patients (median age, 63 years; range, 22 to 79 years), after a median follow-up of 50.4 months, 197 patients had relapsed and 36 had received HPC infusion as salvage autoHCT (n = 29) and/or HPC boost (n = 8). In this cohort, a median CD34+ cell dose of 4.3 × 106/kg (range, 1.1 to 12.94.3 × 106/kg) was used for first autoHCT, and a median of 4.4 × 106/kg (range, 1.0 to 20.2× 106/kg) CD34+ cells were stored for future use. At 6 years after the first autoHCT, the estimated cumulative incidence of salvage autoHCT was 12.0% without HPC boost and 13.9% with HPC boost. HPC utilization was significantly higher in the 60- to 64-year age group, whereas no patients who were age ≥70 years at the time of first autoHCT received salvage autoHCT. Using the CD34+ cell dose infused during the first autoHCT as the cutoff for individual patients, the estimated mean additional cost of HPC collection intended for subsequent use (over and above the HPCs used for first autoHCT) was $10,795 ($4.32 million for the entire cohort), an estimated 14% of which (ie, $583,600) was actually used up in salvage autoHCT by 6 years from first autoHCT. In conclusion, our results suggest the need for reappraisal of HPC collection targets for salvage autoHCT and argue against HPC collection and storage for salvage autoHCT in patients age ≥70 years at the time of first autoHCT.

Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma.

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.

Cost and efficacy of peripheral stem cell mobilization strategies in multiple myeloma.

Mobilization of peripheral blood stem cells (PBSC) can be performed using plerixafor, which is expensive, or high-dose cyclophosphamide (HDCy). We hypothesized that the overall cost of mobilization with plerixafor might not be greater if the cost of complication management was considered. We performed a cost analysis of these two strategies. This multicentric observational study recruited patients with myeloma who underwent a first PBSC mobilization. We considered direct medical costs, including hospitalization, mobilization agents, apheresis, and supportive treatments. We included 111 patients, 54 and 57 in the HDCy and plerixafor groups, respectively. Cost of mobilization with HDCy was 5097 ± 2982€ vs. 10958 ± 1789€ for plerixafor (p < 0.0001). Cost of agents used was 1287 ± 779€ vs. 6552 ± 509€, respectively (p = 0.0009). The mean number of days of hospitalization was 2 and 2.1 days, respectively (p = 0.035). All patients achieved the minimum PBSC collection target (p = 1.0); however, ASCT was performed with HDCy in 67% patients and with plerixafor in 86% (p = 0.02). Plerixafor mobilization incurred a greater cost, mostly due to the greater cost of the drug. Hospitalization length in the two groups was similar in our series. Interestingly, plerixafor appeared to be a very effective and safe mobilizing approach translating into a greater ASCT success.

Assessment and streamlined preparation of low-cytotoxicity lentiviral vectors for mobilized human hematopoietic stem cell transduction.

As important vectors for ectopic protein expression, gene silencing, and progenitor cell barcoding, lentiviruses continue to emerge as versatile research and clinical tools. For studies employing cell types that are relatively resistant to transduction, high-titer lentivirus preparations with low cytotoxicity are required. During lentivirus production, carryover plasmid DNA endotoxins, transfection reagents, damaged packaging cells, and virus concentration procedures are potential sources of cytotoxicity. As an often unevaluated property of lentivirus preparations, cytotoxicity can unwittingly skew estimates of functional titers and complicate interpretations of transduced cell phenotypes. By employing hematopoietic UT7epo cells cultured in erythropoietin (EPO) below maximal dosing, we first define a sensitive flow cytometric bioassay for critically assessing the cytotoxicity (and titers) of lentivirus preparations. Bioassay of custom preparations of research-grade lentiviruses from six commercial sources unexpectedly revealed substantial cytotoxicity (with certain preparations additionally registering titers several log below designated values). To overcome such limiting properties, we further report on unique, efficient workflows for reproducibly preparing and processing high-titer, low-cytotoxicity (HTLC) lentiviruses at research scale. These HTLC lentiviruses reliably transduce peripheral blood hematopoietic stem/progenitor cells (PB-HSPCs) at frequencies ≥40%, with low cytotoxicity. In addition, by employing cyclosporin H (to inhibit IFITM3), PB-HSPCs can be transduced at heightened efficiency with nominal cytotoxicity. Overall, this work provides straightforward approaches to (1) critical assessment of the cytotoxicity of lentivirus preparations; (2) reproducible generation (and concentration) of high-quality lentiviruses via a streamlined workflow; and (3) transduction of PB-HSPCs at benchmark levels with nominal cytotoxicity.

Tbo-filgrastim versus filgrastim for stem cell mobilization and engraftment in autologous hematopoietic stem cell transplant patients: A retrospective review.

INTRODUCTION: Filgrastim, a granulocyte colony-stimulating factor, is commonly used in autologous hematopoietic stem cell transplants (HSCTs) to assist with peripheral blood progenitor cell (PBPC) collection and to support stem cell engraftment. In the United States, tbo-filgrastim is approved under its own Biologic License Application and is limited to a single indication excluding the HSCT population. METHODS: Approximately one year after a system-wide formulary change to tbo-filgrastim for all on- and off-label indications, our institution conducted an IRB-approved retrospective comparison of tbo-filgrastim to filgrastim in the autologous HSCT setting. The study included 71 patients who received an autologous HSCT from 1 January 2013 to 31 December 2016 with a documented administration of tbo-filgrastim or filgrastim. RESULTS: There were no statistically significant differences noted on CD34 + counts during stem cell mobilization, neutrophil engraftment, infection rates during the engraftment phase, nor duration of hospitalization during the engraftment phase. More patients in the tbo-filgrastim group received plerixafor per protocol resulting in more patients meeting their PBPC collection goal in one day with fewer collection days overall, a result potentially confounded by institutional protocol changes. Utilizing tbo-filgrastim offered an average cost savings per patient of $2664.26 ($1907.33 for PBPC mobilization and $756.93 for stem cell engraftment) when comparing dollars spent on granulocyte colony-stimulating factor products only. CONCLUSION: Tbo-filgrastim demonstrates comparable efficacy with a cost savings benefit compared to filgrastim for autologous PBPC mobilization and stem cell engraftment.

Evaluation of a biosimilar granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in Japanese healthy donors: a prospective study.

A "biosimilar" is a biotechnological product with a lower cost profile and equivalent efficacy and safety to the originator, but post-marketing clinical evaluation of biosimilar products has not been adequately conducted. We prospectively investigated the utility of biosimilar filgrastim in 13 peripheral blood stem cell (PBSC) donors from June 2014 to January 2017. In addition, we retrospectively compared these to another 13 PBSC donors mobilized with the originator filgrastim in the same period. Donor characteristics were equivalent between the groups. The median number of CD34+ cells per donor body weight (BW) and blood volume processed (BV) were 4.87 × 106/kg and 25.5 × 103/mL in the biosimilar group and 4.93 × 106/kg and 16.6 × 103/mL in the originator group, respectively. There were no significant differences between the groups in the number of CD34+ cells per donor BW or BV. All adverse events associated with G-CSF were permissive. The total G-CSF cost was significantly lower in the biosimilar group than in the originator group. These findings suggest that biosimilar filgrastim has the same efficacy and short-term safety as originator filgrastim for PBSC mobilization in healthy donors, with economic superiority. Longer follow-up studies are needed to evaluate the incidence of long-term adverse events.