Economic evaluation of treosulfan in patients undergoing allogeneic haematopoietic stem cell transplantation
DOI:
https://doi.org/10.33393/grhta.2022.2412Keywords:
Acute Myeloid Leukemia, Myelodysplastic Syndrome, alloHSCT, TreosulfanAbstract
Objective. To assess the cost-effectiveness and economic sustainability of treosulfan plus fludarabine compared with busulfan plus fludarabine as a conditioning treatment for malignant disease prior to allogeneic haematopoietic stem cell transplantation (alloHSCT) in adult patients in Italy.
Method. The two theoretical cohorts of patients aged ≥ 60 years with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) were pooled and followed over time using a partitioned survival model with cycles of 28 days. Patients can transition between a post-HSCT recovery/remission state (Event-Free Survival state, EFS state), a relapsed/progressed disease state, and a death state. A lifetime horizon for cost-effectiveness analysis and a 5-years’ time horizon for budget impact analysis were used. The perspective of the Italian National Health Service was adopted. Utility values were obtained from published sources. Costs included: drug acquisition, HSCT procedure, management and treatment of adverse reactions, graft-versus-host disease (GvHD) and health states, end of life treatment. Discounting of 3% per year was applied for both costs and outcomes according to Italian guidelines. Sensitivity was tested through both one-way and probabilistic analyses.
Results. Cost-effectiveness analysis showed that treosulfan is both more effective and less expensive compared with busulfan (+1.11 life-years, +0.96 quality-adjusted life-years per patient and -€ 41,784 per patient). On the side of economic sustainability, the introduction of treosulfan in the market could generate a cumulative decrement of the expense incurred by NHS of about -€ 179,174 over five years.
Conclusion. Treosulfan could represent a cost-effective and sustainable treatment alternative from the perspective of the NHS.
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References
Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344-353. https://doi.org/10.1182/blood-2014-02-514778 PMID:24914142 DOI: https://doi.org/10.1182/blood-2014-02-514778
Kröger N, Solano C, Wolschke C, et al. Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease. N Engl J Med. 2016;374(1):43-53. https://doi.org/10.1056/NEJMoa1506002 PMID:26735993 DOI: https://doi.org/10.1056/NEJMoa1506002
Gratwohl A. The EBMT risk score. Bone Marrow Transplant. 2012;47(6):749-756. https://doi.org/10.1038/bmt.2011.110 PMID:21643021 DOI: https://doi.org/10.1038/bmt.2011.110
D’Souza A, Fretham C. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides. 2018; Online https://www.cibmtr.org. (Accessed March 2022)
Kröger, N., D.W. Beelen, and D.A.f.K.-u.B.e.V. für die DAG-KBT. Conditioning. Allogeneic stem cell transplantation [In German]. 2018; Online: https://www.onkopedia.com/de/onkopedia/guidelines/allgemeine-anforderungen/@@guideline/html/index.html. (Accessed March 2022)
Gorin NC, Labopin M, Boiron JM, et al; Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation. Results of genoidentical hemopoietic stem cell transplantation with reduced intensity conditioning for acute myelocytic leukemia: higher doses of stem cells infused benefit patients receiving transplants in second remission or beyond--the Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2006;24(24):3959-3966. https://doi.org/10.1200/JCO.2006.05.5855 PMID:16880451 DOI: https://doi.org/10.1200/JCO.2006.05.5855
Kröger N, Bornhäuser M, Ehninger G, et al; German Cooperative Transplant Study Group. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol. 2003;82(6):336-342. https://doi.org/10.1007/s00277-003-0654-9 PMID:12728337 DOI: https://doi.org/10.1007/s00277-003-0654-9
Beelen DW, Trenschel R, Stelljes M, et al., Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol, 2020. 7(1): e28-e39. https://doi.org/10.1016/s2352-3026(19)30157-7 PMID: 31606445 DOI: https://doi.org/10.1016/S2352-3026(19)30157-7
Beelen DW, Trenschel R, Stelljes M, et al. Final Results of a Prospective Randomized Multicenter Phase III Trial Comparing Treosulfan/Fludarabine to Reduced Intensity Conditioning with Busulfan/Fludarabine Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Elderly or Comorbid Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome. Blood 2017; 130 (S1): 521. https://doi.org/10.1182/blood.V130.Suppl_1.521.521
Associazione Italiana di Economia Sanitaria. Proposta di Linee-Guida per la valutazione economica degli interventi sanitari. Poilitiche Sanitarie. 2009;10(2):91-99. Online https://www.politichesanitarie.it/r.php?v=441&a=5195&l=4896&f=allegati/00441_2009_02/fulltext/05.Lineeguida%20(91-99).pdf (Accessed March 2022)
CHEERS 2022 Checklist, Online: https://www.equator-network.org/wp-content/uploads/2013/04/CHEERS-2022-checklist-1.pdf. (Accessed March 2022)
Riunione Nazionale GITMO - Bologna 06 / 07 maggio 2019. Volume redatto dalla Segreteria Scientifica e di Presidenza con il contributo dei referenti delle attività GITMO, DataBase Nazionale, CNT e IBMDR. Online https://www.gitmo.it/storage/gitmo/article/pdf/36/1-libro-gitmo-019.pdf (Accessed March 2022)
National Institute fo Health and Care Excellence. Single Technology Appraisal Treosulfan with fludarabine for malignant disease before allogeneic stem cell transplant [ID1508]. Online: https://www.nice.org.uk/guidance/ta640/evidence/appraisal-consultation-committee-papers-pdf-8828294941. (Accessed March 2022)
National Institute for Health and Care Excellence Decision Support Unit (NICE DSU), TSD 14: Survival analysis for economic evaluations alongside clinical trials – extrapolation with patient-level data. Online https://www.ncbi.nlm.nih.gov/books/NBK395885/pdf/Bookshelf_NBK395885.pdf (Accessed March 2022)
Martin PJ, Counts GW Jr, Appelbaum FR, et al. Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. J Clin Oncol. 2010;28(6):1011-1016. https://doi.org/10.1200/JCO.2009.25.6693 PMID:20065176 DOI: https://doi.org/10.1200/JCO.2009.25.6693
National Institute for Health and Care Excellence (NICE). TA552: Liposomal cytarabine–daunorubicin for untreated acute myeloid leukaemia. Technology Appraisal Guidance (2018). Online: https://www.nice.org.uk/guidance/ta552. (Accessed March 2022)
NICE. Single technology appraisal. Treosulfan with fludarabine for malignant disease before allogeneic stem cell transplant [ID1508]. Document B. Company evidence submission. May 2019. Online https://www.nice.org.uk/guidance/ta640/evidence/appraisal-consultation-committee-papers-pdf-8828294941 (Accessed March 2022)
Grulke N, Albani C, Bailer H. Quality of life in patients before and after haematopoietic stem cell transplantation measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30. Bone Marrow Transplant. 2012;47(4):473-482. https://doi.org/10.1038/bmt.2011.107 PMID:21602898 DOI: https://doi.org/10.1038/bmt.2011.107
Proskorovsky I, Lewis P, Williams CD, et al. Mapping EORTC QLQ-C30 and QLQ-MY20 to EQ-5D in patients with multiple myeloma. Health Qual Life Outcomes. 2014;12(1):35. https://doi.org/10.1186/1477-7525-12-35 PMID:24618388 DOI: https://doi.org/10.1186/1477-7525-12-35
National Institute for Health and Care Excellence (NICE). TA545: Gemtuzumab ozogamicin for untreated acute myeloid leukaemia. Online: https://www.nice.org.uk/guidance/ta545. (Accessed March 2022)
National Institute for Health and Care Excellence (NICE). TA399: Azacitidine for treating acute myeloid leukaemia with more than 30% bone marrow blasts. 2016 [cited 2019 17th April ]; Online: https://www.nice.org.uk/guidance/ta399. (Accessed Mach 2022)
Kurosawa S, Yamaguchi H, Yamaguchi T, et al. Decision Analysis of Postremission Therapy in Cytogenetically Intermediate-Risk Acute Myeloid Leukemia: The Impact of FLT3 Internal Tandem Duplication, Nucleophosmin, and CCAAT/Enhancer Binding Protein Alpha. Biol Blood Marrow Transplant. 2016;22(6):1125-1132. https://doi.org/10.1016/j.bbmt.2016.03.015PMID:27040395 DOI: https://doi.org/10.1016/j.bbmt.2016.03.015
Decreto del Ministero della Salute 18 ottobre 2012, Tariffe delle prestazioni di assistenza specialistica ambulatoriale.; Online: https://www.trovanorme.salute.gov.it/norme/renderPdf.spring?seriegu=SG&datagu=28/01/2013&redaz=13A00528&artp=3&art=1&subart=1&subart1=10&vers=1&prog=001. (Accessed March 2022)
Robin C, Hémery F, Dindorf C, et al. Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients. BMC Infect Dis. 2017;17(1):747. https://doi.org/10.1186/s12879-017-2854-2PMID:29207952 DOI: https://doi.org/10.1186/s12879-017-2854-2
Decreto del Ministero della Salute 18 ottobre 2012, Tariffe delle prestazioni di assistenza ospedaliera per acuti, per tipo di ricovero. Online: https://www.trovanorme.salute.gov.it/norme/renderPdf.spring?seriegu=SG&datagu=28/01/2013&redaz=13A00528&artp=1&art=1&subart=1&subart1=10&vers=1&prog=001. (Accessed March 2022)
Johnston K, Levy AR, Lorigan P, et al. Economic impact of healthcare resource utilisation patterns among patients diagnosed with advanced melanoma in the United Kingdom, Italy, and France: results from a retrospective, longitudinal survey (MELODY study). Eur J Cancer. 2012;48(14):2175-2182. https://doi.org/10.1016/j.ejca.2012.03.003 PMID:22480965 DOI: https://doi.org/10.1016/j.ejca.2012.03.003
Mickisch G, Gore M, Escudier B, Procopio G, Walzer S, Nuijten M. Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-alpha2a compared with sunitinib. Br J Cancer. 2010;102(1):80-86. https://doi.org/10.1038/sj.bjc.6605417 PMID:19920817 DOI: https://doi.org/10.1038/sj.bjc.6605417
Wehler E, Zhao Z, Pinar Bilir S, Munakata J, Barber B. Economic burden of toxicities associated with treating metastatic melanoma in eight countries. Eur J Health Econ. 2017;18(1):49-58. https://doi.org/10.1007/s10198-015-0757-y PMID:26721505 DOI: https://doi.org/10.1007/s10198-015-0757-y
Lazzaro C, Bordonaro R, Cognetti F, et al. An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) versus conventional paclitaxel for metastatic breast cancer patients: the COSTANza study. Clinicoecon Outcomes Res. 2013;5:125-135. https://doi.org/10.2147/CEOR.S41850 PMID:23610525 DOI: https://doi.org/10.2147/CEOR.S41850
Favaretto A, Grossi F, Morabito A, Ravasio R. Il costo degli eventi avversi associati ad afatinib, erlotinib e gefitinib nel trattamento del tumore del polmone non a piccole cellule con mutazione EGFR. Glob Reg Health Technol Assess. 2017;4(1):e187-e196. https://doi.org/10.5301/grhta.5000270 DOI: https://doi.org/10.5301/grhta.5000270
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Accepted 2022-09-06
Published 2022-10-05
