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Economic evaluation of plerixafor addition in the mobilization and leukapheresis of hematopoietic stem cells for autologous transplantation: a systematic review
Mesquita Augusto Passos, R., Feldens, T. K., Marcolino, M. A. Z., Gouvêa, A. S., Dos Santos Oliveira, L., Menardi, L., Rodrigues, R. F., de Lourdes Martins Perobelli, L., Campolina, A. G., de Almeida Neto, C.
Expert review of pharmacoeconomics & outcomes research. 2022
Abstract
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 June 30, 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 cut-offs 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.
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Plerixafor in combination with chemotherapy and/or hematopoietic cell transplantation to treat acute leukemia: A systematic review and metanalysis of preclinical and clinical studies
Maganti, H., Visram, A., Shorr, R., Fulcher, J., Sabloff, M., Allan, D. S.
Leukemia research. 2020;97:106442
Abstract
Leukemia-initiating cells localize to bone marrow niches via cell surface CXCR4 binding to stromal-derived factor 1 (SDF-1). Plerixafor, a CXCR4 antagonist, can mobilize and sensitize leukemia cells to cytotoxic therapy, and/or enhance the engraftment of healthy donor stem cells in the context of hematopoietic cell transplantation (HCT). A systematic review of preclinical and clinical studies was performed (updated May 1, 2020) to inform the design of definitive clinical trials and identified 19 studies. Pooled data from 10 preclinical in-vivo studies of AML and ALL in mouse models of leukemia revealed significant mobilization of leukemia cells into the peripheral circulation, decreased total blast burden and increased survival with plerixafor in addition to cytotoxic treatment compared to control animals. Two of 9 clinical studies compared outcomes to a control group. Plerixafor appears well tolerated and safe and can mobilize leukemia cells into the peripheral circulation. In patients with AML undergoing HCT, plerixafor given with the conditioning regimen appears safe and well tolerated. Engraftment, relapse and survival were not different from controls after limited follow-up. Studies in high risk patients with AML with longer follow-up are needed to understand the influence on relapse following treatment and on donor cell engraftment following HCT.
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Efficacy and safety of plerixafor for hematopoietic stem cell mobilization for autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma: A systematic review and meta-analysis
Yang, X., Wan, M., Yu, F., Wang, Z.
Experimental and therapeutic medicine. 2019;18(2):1141-1148
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Abstract
Plerixafor in combination granulocyte-colony stimulating factor (G-CSF) has been used for the mobilization of hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). The aim of this study was to systematically search the published literature and analyze evidence on the efficacy of additional plerixafor for successful HSC mobilization in patients with NHL and MM, and to evaluate the safety of the drug. The PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and Google scholar databases were searched electronically for studies published in the English language up to March, 2019. Five studies (3 on NHL and 2 on MM) were included in this review article. The meta-analysis of data of 364 patients in the treatment group and 368 patients in the control group, indicated that the mobilization of ≥5/6x10(6) CD34(+) cells/kg in 4 or less apheresis days was superior with plerixafor + G-CSF than with G-CSF alone (RR=2.59, 95% CI: 1.40 to 4.81; P<0.0001). Similarly, a greater proportion of patients in the treatment group exhibited the mobilization of ≥2x10(6) CD34(+) cells/kg in 4 or less apheresis days (RR=1.46, 95% CI: 1.01 to 2.12; P=0.04). The addition of plerixafor significantly increased the total collection of CD34(+) cells (random: MD=4.21; 95% CI: 2.85 to 5.57; P<0.00001). Meta-analysis indicated no significant increase in adverse events with the addition of plerixafor for HSC mobilization (RR=1.03, 95% CI: 0.99 to 1.06; P=0.16). On the whole, the findings of this study indicate that the addition of plerixafor to G-CSF leads to an increased HSC collection in a shorter period of time with no concomitant increase in adverse events. Further randomized controlled trials with a larger sample size evaluating short term efficacy, as well as long term survival would help to further strengthen the evidence on this subject.
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Current use of biosimilar G-CSF for haematopoietic stem cell mobilisation
Pahnke, S., Egeland, T., Halter, J., Hagglund, H., Shaw, B. E., Woolfrey, A. E., Szer, J.
Bone marrow transplantation. 2018
Abstract
Despite biosimilars of the granulocyte-colony stimulating factor (G-CSF) filgrastim being approved by the European Medicines Agency since 2008, there is still some debate regarding their use in related and unrelated healthy haematopoietic stem cell donors. We present a review of published experiences using biosimilar filgrastim for healthy donor mobilisation as well as the results of a survey by the World Marrow Donor Association (WMDA) of its current use by register-associated transplant and collection centres for both related and unrelated donors. A total of 1287 healthy donors and volunteers are included in the reviewed studies. The pharmacokinetics and pharmacodynamics studies show a high degree of similarity to the reference product Neupogen. Mobilisation of CD34 + cells as well as reported adverse events are also found to be comparable, although there is still a lack of long-term follow up for both Neupogen and filgrastim biosimilars. No evidence is found of a higher risk of filgrastim antibody formation using filgrastim biosimilars. Based on this increased experience, the WMDA therefore recommend that Stem Cell Donor Registries can use filgrastim biosimilars for the mobilisation of peripheral blood progenitor cells in healthy donors, provided that they are approved by national and/or regional agencies.
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Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario
Kouroukis, C. T., Varela, N. P., Bredeson, C., Kuruvilla, J., Xenocostas, A.
Current Oncology. 2016;23(4):e409-30
Abstract
BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10-18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. METHODS The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS These recommendations apply to adult patients considered for asct: Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available. For patients with a low peripheral blood CD34+ cell count (for example, <10/muL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization. It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.
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Mobilization of autologous and allogeneic peripheral blood stem cells for transplantation in haematological malignancies using biosimilar G-CSF
Schmitt, M., Hoffmann, J. M., Lorenz, K., Publicover, A., Schmitt, A., Nagler, A.
Vox Sanguinis. 2016;111(2):178-86
Abstract
BACKGROUND AND OBJECTIVES Biosimilars of the granulocyte colony stimulating factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA) for registered indications of the originator G-CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G-CSF. MATERIALS AND METHODS This article is a meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases. All data sets were weighted for the number of patients and parameters and then subjected to statistical meta-analysis employing the Mann-Whitney U-test followed by the Hodges-Lehmann estimator to assess differences between biosimilar and originator G-SCF. RESULTS A total of 1892 individuals, mostly with haematological malignancies but also including 351 healthy donors have been successfully mobilized for autologous or allogeneic stem cell transplantation using biosimilar G-CSF (Zarzio(TM) : 1239 individuals; Ratiograstim(TM) /Tevagrastim(TM) : 653 individuals). A total of 740 patients with multiple myeloma, 491 with non-Hodgkin's lymphoma (NHL), 150 with Hodgkin's lymphoma (HL) and other diseases are included in this meta-analysis, as well as 161 siblings and 190 volunteer unrelated donors. For biosimilar and originator G-CSF, bioequivalence was observed for the yield of CD34+ stem cells as well as for the engraftment of the transplants. CONCLUSION Biosimilar G-CSF has equivalent effects and safety as originator G-CSF. Copyright © 2016 International Society of Blood Transfusion.
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Additional plerixafor to granulocyte colony-stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma
Hartmann, T., Hübel, K., Monsef, I., Engert, A., Skoetz, N.
The Cochrane Database of Systematic Reviews. 2015;2015(10):Cd010615
Abstract
BACKGROUND Autologous stem cell transplantation is widely used to restore functioning bone marrow in people with malignant lymphoma or multiple myeloma after myeloablative chemotherapy. Results of some clinical trials indicate that plerixafor in addition to granulocyte colony-stimulating factors (G-CSF) compared to G-CSF only could lead to an increased mobilisation and release of CD34-positive cells, facilitating effective apheresis. OBJECTIVES To evaluate the efficacy and safety of additional plerixafor to G-CSF for haematopoietic stem cell mobilisation in people with malignant lymphoma or multiple myeloma. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1990 to September 2015), as well as conference proceedings (American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; American Society for Blood and Marrow Transplantation; European Group for Blood and Marrow Transplantation) for studies. Two review authors independently screened search results. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing plerixafor in addition to G-CSF compared to G-CSF only for stem cell mobilisation in people with malignant lymphoma or multiple myeloma of all stages and ages. We included full text as well as abstracts and unpublished data if sufficient information on study design, participant characteristics, interventions, and outcomes was available. We excluded cross-over trials, quasi-randomised trials, and post-hoc retrospective trials. DATA COLLECTION AND ANALYSIS Two review authors independently screened the results of the search strategies, extracted data, assessed quality, and analysed data according to standard Cochrane methods. We performed final interpretation with an experienced clinician. MAIN RESULTS We identified four RCTs fitting the inclusion criteria. However, two of these closed prematurely due to low recruitment and did not report results. The remaining two trials evaluated 600 participants with multiple myeloma or non-Hodgkin lymphoma. In both studies the experimental group received G-CSF plus plerixafor and the control group received G-CSF plus placebo.The meta-analysis showed no evidence for differences between plerixafor and placebo group regarding mortality at 12 months (600 participants; risk ratio (RR) 1.00, 95% confidence interval (CI) 0.59 to 1.69; P = 1.00; moderate-quality evidence) and adverse events during stem cell mobilisation and collection (593 participants; RR 1.02, 95% CI 0.99 to 1.06; P = 0.19; high-quality evidence).Regarding the outcome successful stem cell collection, the meta-analysis showed an advantage for those participants randomised to the plerixafor group (600 participants; RR 2.42, 95% CI 1.98 to 2.96; P < 0.00001; high-quality evidence).As there was high heterogeneity between studies for the number of transplanted participants, we did not meta-analyse these data. In the multiple myeloma study, 95.9% (142 participants) in the plerixafor arm and 88.3% (136 participants) in the placebo arm underwent transplantation (RR 1.09, 95% CI 1.02 to 1.16); in the non-Hodgkin lymphoma trial, 90% (135 participants) in the plerixafor group versus 55.4% (82 participants) in the placebo group could be transplanted (RR 1.62, 95% CI 1.39 to 1.89). In both trials there was no evidence for a difference between participants in the plerixafor and placebo group in terms of time to neutrophil and platelet engraftment in transplanted participants.None of the trials reported on the outcomes quality of life and progression-free survival. AUTHORS' CONCLUSIONS The results of the analysed data suggest that additional plerixafor leads to increased stem cell collection in a shorter time. There was insufficient evidence to determine whether additional plerixafor affects survival or adverse events.The two trials included in the meta-analysis, both of which were conducted by the Genzyme Corporation, the manufacturer of plerixafor, were published several times. Two more RCTs examining the addition of plerixafor to a G-CSF mobilisation regimen terminated early without publishing any outcome. The trials included nine and five participants, respectively. Another RCT with 100 participants was recently completed, but has not yet published outcomes. Due to the unpublished RCTs, it is possible that our review is affected by publication bias, even though two trials failed to recruit a sufficient number of participants to analyse any data.
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Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies
Sheppard, D., Bredeson, C., Allan, D., Tay, J.
Biology of Blood & Marrow Transplantation. 2012;18(8):1191-203
Abstract
Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation; however, a proportion of patients fail to collect the minimum number of cells required. We summarized the efficacy and safety of HSC mobilization strategies. We performed a systematic review of randomized controlled trials comparing HSC mobilization strategies before autologous transplantation for hematologic malignancies. The primary outcome was CD34+ cell yield. Secondary outcomes included number of aphereses, proportion of failures, rate of count recovery, and adverse events. We identified 28 articles within 3 broad strategies. Using a cyclophosphamide with growth factor strategy (10 articles), CD34+ cell yield is improved by addition of molgramostim to cyclophosphamide (1.4 vs 0.5 x 10(6)/kg; P = .0165), addition of cyclophosphamide to filgrastim (7.2 vs 2.5 x 10(6)/kg; P = .004), and addition of ancestim to cyclophosphamide and filgrastim (12.4 vs 8.3 x 10(6)/kg; P = .007). Within a growth factor-based strategy (6 articles), addition of plerixafor improves CD34+ cell yield over filgrastim alone in multiple myeloma (MM; 11.0 vs 6.2 x 10(6)/kg; P < .001) and non-Hodgkin lymphoma (5.69 vs 1.98 x 10(6)/kg; P < .01). With combination or noncyclophosphamide-based chemotherapy (12 articles), higher-dose filgrastim (8.2 vs 4.7 x 10(6)/kg for 16 vs 8/mcg/kg daily of filgrastim, respectively; P < .0001) and addition of rituximab to etoposide and filgrastim (9.9 vs 5.6 x 10(6)/kg; P = .021) improve CD34+ cell yield. Growth factor alone after chemotherapy, ancestim, or plerixafor provide adequate autologous HSC grafts for the majority of patients. Although some strategies result in higher CD34+ cell yield, this potentially comes at the expense of increased toxicity. As all strategies are reasonable, programmatic, and patient-specific considerations must inform the approach to autologous graft mobilization. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.