Top

The European Journal of Health Economics

Published in:

01-06-2020 | Acute Myeloid Leukemia | Original Paper

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

Authors: Gabriel Tremblay, Clemence Cariou, Christian Recher, Mike Dolph, Patricia Brandt, Anne-Sandrine Blanc, Anna Forsythe

Published in: The European Journal of Health Economics | Issue 4/2020

Abstract

Background

Midostaurin (MIDO) combined with standard chemotherapy was approved by the European Medicines Agency in 2017 for the treatment of adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) based on results from the RATIFY trial.

Methods

A cost-effectiveness model was developed to compare MIDO and standard-of-care (SOC) to SOC alone in France. Per Haute Autorité de Santé (HAS) guidelines, a partitioned survival model with eight health states was used: diagnosis/induction, complete remission, relapse, hematopoietic stem cell transplantation (HSCT), HSCT recovery, post-HSCT recovery (stabilized after HSCT recovery), post-HSCT relapse, and mortality. A lifetime horizon was used beginning at diagnosis with a “cure model,”, which assumed natural mortality after trial cut-off. Utility values were obtained from a systematic literature review and included disutilities. Resource utilization was based on HAS clinical guidelines and a survey of French physicians and included drugs and administration, adverse events, routine medical care, HSCT, and end-of-life care costs.

Results

In RATIFY and after extrapolation, MIDO improved survival compared to SOC, translating into MIDO-treated patients gaining 1.12 life years (LYs) and 1.23 quality-adjusted life years (QALYs) versus SOC. The incremental cost-effectiveness ratio (ICER) for MIDO versus SOC was €68,781 per LY and €62,305 per QALY. Sensitivity analyses showed consistency with base case findings.

Conclusions

MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment.

Available only for authorised users

Visser, O., Trama, A., Maynadie, M., Stiller, C., Marcos-Gragera, R., De Angelis, R., Mallone, S., Tereanu, C., Allemani, C., Ricardi, U., Schouten, H.C.: Incidence, survival and prevalence of myeloid malignancies in Europe. Eur. J. Cancer 48(17), 3257–3266 (2012). https://doi.org/10.1016/j.ejca.2012.05.024 CrossRefPubMed

Khan, I., Altman, J.K., Licht, J.D.: New strategies in acute myeloid leukemia: redefining prognostic markers to guide therapy. Clin. Cancer Res. 18(19), 5163–5171 (2012). https://doi.org/10.1158/1078-0432.CCR-12-0313 CrossRefPubMedPubMedCentral

Sant, M., Minicozzi, P., Mounier, M., Anderson, L.A., Brenner, H., Holleczek, B., Marcos-Gragera, R., Maynadie, M., Monnereau, A., Osca-Gelis, G., Visser, O., De Angelis, R.: Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study. Lancet Oncol. 15(9), 931–942 (2014). https://doi.org/10.1016/s1470-2045(14)70282-7 CrossRefPubMed

Maynadie, M., De Angelis, R., Marcos-Gragera, R., Visser, O., Allemani, C., Tereanu, C., Capocaccia, R., Giacomin, A., Lutz, J.M., Martos, C., Sankila, R., Johannesen, T.B., Simonetti, A., Sant, M., Group, H.W.: Survival of European patients diagnosed with myeloid malignancies: a HAEMACARE study. Haematologica 98(2), 230–238 (2013). https://doi.org/10.3324/haematol.2012.064014 CrossRef

Meyers, J., Yu, Y., Kaye, J.A., Davis, K.L.: Medicare fee-for-service enrollees with primary acute myeloid leukemia: an analysis of treatment patterns, survival, and healthcare resource utilization and costs. Appl. Health Econ. Health Policy 11(3), 275–286 (2013). https://doi.org/10.1007/s40258-013-0032-2 CrossRefPubMed

Almeida, A.M., Ramos, F.: Acute myeloid leukemia in the older adults. Leukemia Res. Rep. 6, 1–7 (2016). https://doi.org/10.1016/j.lrr.2016.06.001 CrossRef

Erba, H.P.: Prognostic factors in elderly patients with AML and the implications for treatment. Hematology. American Society of Hematology. Education Program, pp. 420–428 (2007). https://doi.org/10.1182/asheducation-2007.1.420

Patel, J.P., Gonen, M., Figueroa, M.E., Fernandez, H., Sun, Z., Racevskis, J., Van Vlierberghe, P., Dolgalev, I., Thomas, S., Aminova, O., Huberman, K., Cheng, J., Viale, A., Socci, N.D., Heguy, A., Cherry, A., Vance, G., Higgins, R.R., Ketterling, R.P., Gallagher, R.E., Litzow, M., van den Brink, M.R., Lazarus, H.M., Rowe, J.M., Luger, S., Ferrando, A., Paietta, E., Tallman, M.S., Melnick, A., Abdel-Wahab, O., Levine, R.L.: Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N. Engl. J. Med. 366(12), 1079–1089 (2012). https://doi.org/10.1056/NEJMoa1112304 CrossRefPubMedPubMedCentral

Schiller, G.J.: High-risk acute myelogenous leukemia: treatment today and tomorrow. Hematology. American Society of Hematology. Education Program 2013, pp. 201–208 (2013). https://doi.org/10.1182/asheducation-2013.1.201

10.

Milligan, D.W., Grimwade, D., Cullis, J.O., Bond, L., Swirsky, D., Craddock, C., Kell, J., Homewood, J., Campbell, K., McGinley, S., Wheatley, K., Jackson, G.: Guidelines on the management of acute myeloid leukaemia in adults. Br. J. Haematol. 135(4), 450–474 (2006). https://doi.org/10.1111/j.1365-2141.2006.06314.x CrossRefPubMed

11.

Zeiser, R., Blazar, B.R.: Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N. Engl. J. Med. 377(26), 2565–2579 (2017). https://doi.org/10.1056/NEJMra1703472 CrossRefPubMed

12.

Kuba, A., Raida, L.: Graft versus host disease: from basic pathogenic principles to DNA damage response and cellular senescence. Mediat. Inflamm. 2018 (2018). https://doi.org/10.1155/2018/9451950

13.

Jagasia, M., Arora, M., Flowers, M.E., Chao, N.J., McCarthy, P.L., Cutler, C.S., Urbano-Ispizua, A., Pavletic, S.Z., Haagenson, M.D., Zhang, M.J., Antin, J.H., Bolwell, B.J., Bredeson, C., Cahn, J.Y., Cairo, M., Gale, R.P., Gupta, V., Lee, S.J., Litzow, M., Weisdorf, D.J., Horowitz, M.M., Hahn, T.: Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 119(1), 296–307 (2012). https://doi.org/10.1182/blood-2011-06-364265 CrossRefPubMedPubMedCentral

14.

El Fakih, R., Rasheed, W., Hawsawi, Y., Alsermani, M., Hassanein, M.: Targeting FLT3 mutations in acute myeloid leukemia. Cells 7(1) (2018). https://doi.org/10.3390/cells7010004

15.

Serrano-Blanco, A., Rubio-Valera, M., Aznar-Lou, I., Baladon Higuera, L., Gibert, K., Gracia Canales, A., Kaskens, L., Ortiz, J.M., Salvador-Carulla, L.: In-patient costs of agitation and containment in a mental health catchment area. BMC Psychiatry 17(1), 212 (2017). https://doi.org/10.1186/s12888-017-1373-4 CrossRefPubMedPubMedCentral

16.

Stone, R.M., Manley, P.W., Larson, R.A., Capdeville, R.: Midostaurin: its odyssey from discovery to approval for treating acute myeloid leukemia and advanced systemic mastocytosis. Blood Adv 2(4), 444–453 (2018). https://doi.org/10.1182/bloodadvances.2017011080 CrossRefPubMedPubMedCentral

17.

Lin, T.L., Levy, M.Y.: Acute myeloid leukemia: focus on novel therapeutic strategies. Clinical Medicine Insights. Oncology 6, 205–217 (2012). https://doi.org/10.4137/cmo.s7244 CrossRefPubMed

18.

Stone, R.M., Mandrekar, S., Sanford, B.L., Geyer, S., Bloomfield, C.D., Dohner, K., Thiede, C., Marcucci, G., Lo-Coco, F., Klisovic, R.B., Wei, A., Sierra, J., Sanz, M.A., Brandwein, J.M., de Witte, T., Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Larson, R.A., Dohner, H.: The multi-kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)/cytarabine (C) induction (ind), high-dose C consolidation (consol), and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (AML) patients (pts) age 18–60 with FLT3 mutations (muts): an international prospective randomized (rand) P-controlled double-blind trial (CALGB 10603/RATIFY [Alliance]). Blood 126(23), 6 (2015)CrossRef

19.

Stone, R.M., Mandrekar, S.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Dohner, K., Marcucci, G., Lo-Coco, F., Klisovic, R.B., Wei, A., Sierra, J., Sanz, M.A., Brandwein, J.M., de Witte, T., Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Larson, R.A., Dohner, H.: Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N. Engl. J. Med. (2017). https://doi.org/10.1056/NEJMoa1614359 CrossRefPubMedPubMedCentral

20.

Choix méthodologiques pour l’évaluation économique à la HAS. http://www.has-sante.fr/portail/upload/docs/application/pdf/2011-11/guide_methodo_vf.pdf (2011)

21.

Husereau, D., Drummond, M., Petrou, S., et al.: Consolidated health economic evaluation reporting standards (CHEERS)—explanation and elaboration: a report of the ISPOR Health Economic Evaluations Publication Guidelines Good Reporting Practices Task Force. Value Health. 16(2), 231–250 (2013)CrossRef

22.

Taux de mortalité par sexe et groupe d’âges en 2014. http://www.insee.fr/fr/themes/detail.asp?ref_id=ir-irsocsd2014&page=irweb/irsocsd2014/dd/irsocsd2014_mortalite.htm (2016). 2018

23.

Lebègue D, B.L., Hirtzman P: Révision du taux d’actualisation des investissements publics. In. Commissariat general au Plan (2005)

24.

Base des Médicaments et Informations Tarifaires. http://www.codage.ext.cnamts.fr/codif/bdm_it/index.php (2018). 2018

25.

Cancer Mpact AML Drug Regimen- France 2016. In. Kantar Health, (2016)

26.

Treatment Architecture: Western Europeleukemia, acute myeloid. In: CancerMPact^®Western Europe, 2015 Kantar Health (2015)

27.

Leucémies aiguës de l’adulte: Tumeur maligne, affection maligne du tissu lymphatique ou hématopoïétique. In: GUIDE - AFFECTION DE LONGUE DURÉE. Haute Autorité de Santé, Saint-Denis, France, (2011)

28.

Census Profile, 2016 Census: Ontario [Province] and Canada [Country]. https://www12.statcan.gc.ca/census-recensement/2016/dp-pd/prof/details/Page.cfm?Lang=E&Geo1=PR&Code1=35&Geo2=&Code2=&Data=Count&SearchText=Ontario&SearchType=Begins&SearchPR=01&B1=All&GeoLevel=PR&GeoCode=35 (2016). Accessed June 26 2018

29.

Press, V.G., Pappalardo, A.A., Conwell, W.D., Pincavage, A.T., Prochaska, M.H., Arora, V.M.: Interventions to improve outcomes for minority adults with asthma: a systematic review. J. Gen. Intern. Med. 27(8), 1001–1015 (2012). https://doi.org/10.1007/s11606-012-2058-9 CrossRefPubMedPubMedCentral

30.

Fey, M.F., Buske, C., Group, E.G.W.: Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6), vi138–143 (2013). https://doi.org/10.1093/annonc/mdt320

31.

Dohner, H., Estey, E.H., Amadori, S., Appelbaum, F.R., Buchner, T., Burnett, A.K., Dombret, H., Fenaux, P., Grimwade, D., Larson, R.A., Lo-Coco, F., Naoe, T., Niederwieser, D., Ossenkoppele, G.J., Sanz, M.A., Sierra, J., Tallman, M.S., Lowenberg, B., Bloomfield, C.D., European, L.: Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3), 453–474 (2010). https://doi.org/10.1182/blood-2009-07-235358 CrossRefPubMed

32.

Wingard, J.R., Majhail, N.S., Brazauskas, R., Wang, Z., Sobocinski, K.A., Jacobsohn, D., Sorror, M.L., Horowitz, M.M., Bolwell, B., Rizzo, J.D., Socie, G.: Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J. Clin. Oncol. 29(16), 2230–2239 (2011). https://doi.org/10.1200/jco.2010.33.7212 CrossRefPubMedPubMedCentral

33.

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. 47(4), 473–482 (2012). https://doi.org/10.1038/bmt.2011.107 CrossRefPubMed

34.

Forsythe, A., Brandt, P.S., Dolph, M., Patel, S., Rabe, A.P.J., Tremblay, G.: Systematic review of health state utility values for acute myeloid leukemia. CEOR 10, 83–92 (2018). https://doi.org/10.2147/ceor.s153286 CrossRef

35.

Crott, R., Briggs, A.: Mapping the QLQ-C30 quality of life cancer questionnaire to EQ-5D patient preferences. Eur. J. Health Econ 11(4), 427–434 (2010). https://doi.org/10.1007/s10198-010-0233-7 CrossRefPubMed

36.

Tolley, K., Goad, C., Yi, Y., Maroudas, P., Haiderali, A., Thompson, G.: Utility elicitation study in the UK general public for late-stage chronic lymphocytic leukaemia. Eur. J. Health Econ: HEPAC 14(5), 749–759 (2013). https://doi.org/10.1007/s10198-012-0419-2 CrossRefPubMed

37.

Peric, Z., Desnica, L., Durakovic, N., Ostojic, A., Pulanic, D., Serventi-Seiwerth, R., Prenc, E., Basak, G., Vrhovac, R., Pavletic, S.Z., Nemet, D.: Which questionnaires should we use to evaluate quality of life in patients with chronic graft-vs-host disease? Croat. Med. J. 57(1), 6–15 (2016)CrossRef

38.

Uyl-de Groot, C.A., Lowenberg, B., Vellenga, E., Suciu, S., Willemze, R., Rutten, F.F.: Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukemia. Br. J. Haematol. 100(4), 629–636 (1998)CrossRef

39.

Batty, N., Yin, Y., Wetzler, M.: Decitabine is more cost effective than cytarabine and daunorubicin in elderly acute myeloid leukemia patients. J. Cancer Res. Ther. 2(4), 68–73 (2014). http://dx.doi.org/10.14312/2052-4994.2014-9

40.

Leunis, A., Redekop, W.K., Uyl-de Groot, C.A., Lowenberg, B.: Impaired health-related quality of life in acute myeloid leukemia survivors: a single-center study. Eur. J. Haematol. 93(3), 198–206 (2014). https://doi.org/10.1111/ejh.12324 CrossRefPubMed

41.

Pan, F., Peng, S., Fleurence, R., Linnehan, J.E., Knopf, K., Kim, E.: Economic analysis of decitabine versus best supportive care in the treatment of intermediate- and high-risk myelodysplastic syndromes from a US payer perspective. Clin. Ther. 32(14), 2444–2456 (2010). https://doi.org/10.1016/j.clinthera.2010.12.003 CrossRefPubMed

42.

Briggs, A.H., Weinstein, M.C., Fenwick, E.A., Karnon, J., Sculpher, M.J., Paltiel, A.D., Force, I.-S.M.G.R.P.T.: Model parameter estimation and uncertainty: a report of the ISPOR-SMDM modeling good research practices task force-6. Value Health 15(6), 835–842 (2012). https://doi.org/10.1016/j.jval.2012.04.014

43.

National Institute for Health and Care Excellence. Azacitidine for treating acute myeloid leukaemia with more than 30% bone marrow blasts 27 July 2016. https://www.nice.org.uk/guidance/ta399/chapter/4-Committee-discussion. Accessed 27 Sep 2019

Title: Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France
Authors: Gabriel Tremblay
Clemence Cariou
Christian Recher
Mike Dolph
Patricia Brandt
Anne-Sandrine Blanc
Anna Forsythe
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Acute Myeloid Leukemia
Care
Published in: The European Journal of Health Economics / Issue 4/2020
Print ISSN: 1618-7598
Electronic ISSN: 1618-7601
DOI: https://doi.org/10.1007/s10198-019-01149-9

At a glance: The STEP trials

Springer Medicine

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2020

A general framework for classifying costing methods for economic evaluation of health care

Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients

Biases in health expectancies due to educational differences in survey participation of older Europeans: It’s worth weighting for

Trends in rates of orthopedic surgery in Germany: the good, the bad, and the ugly

A vision ‘bolt-on’ increases the responsiveness of EQ-5D: preliminary evidence from a study of cataract surgery

Patients with coronary artery disease after acute myocardial infarction: effects of continuous enrollment in a structured Disease Management Program on adherence to guideline-recommended medication, health care expenditures, and survival