Cost Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States
The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the treatment of adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective.
A lifetime partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness.
In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY.
This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed FLT3-mutated AML, from a US third-party payer perspective.
Medical writing assistance was provided by Cinzia Metallo, PhD, an employee of Analysis Group, and was ultimately paid for by Novartis Pharmaceuticals Corporation. The authors would like to thank Praveen Gunda, an employee of Novartis Healthcare Pvt. Ltd, for his technical insights.
All authors were involved in the conception and design of the study, analysis and interpretation of the data, drafting of the manuscript, or revising the manuscript critically for intellectual content. All authors approved the final version of the manuscript submitted for publication and agree to be accountable for all aspects of the work.
Compliance with Ethical Standards
This study was funded by Novartis Pharmaceuticals Corporation.
Conflict of interest
Eytan Stein has received consultancy fees and/or research funding from Novartis, Agios Pharmaceuticals, Celgene Corporation, Pfizer, GlaxoSmithKline, Seattle Genetics, and Constellation Pharma. Umakanth Vudumula is an employee of Novartis Healthcare Private Limited. Briana Ndife, Gaetano Bonifacio, and George Joseph are employees of Novartis Pharmaceuticals Corporation and own stock/stock options in the company. Jipan Xie and Annie Guerin are employees of Analysis Group, which has received consultancy fees from Novartis Pharmaceuticals Corporation for this study. Subrata Bhattacharya was an employee of Novartis Healthcare Pvt. Ltd at the time this study was conducted. Nanxin Li and Emilie Duchesneau were employees of Analysis Group at the time this study was conducted.
This study did not involve human participants, therefore no formal consent was required.
Model inputs are described within the article. The model was developed in Microsoft Excel and is not publicly available, but is available from the authors upon reasonable request, with authorization from Novartis Pharmaceuticals Corporation and receipt of a signed confidentiality agreement.
- 2.American Cancer Society. What are the key statistics about acute myeloid leukemia? Available at: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html. Accessed 22 Sep 2018.
- 3.National Cancer Institute. Cancer stat facts: acute myeloid leukemia (AML). 2017. Available at: https://seer.cancer.gov/statfacts/html/amyl.html. Accessed Sep 2017.
- 4.Sotak M, Marin M, Coombs J, Teitelbaum A, editors. The burden of illness (BOI) of FLT3-mutated acute myeloid leukemia in the United States. In: 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 17th Annual International Meeting; Washington, DC.Google Scholar
- 6.Szer J. The prevalent predicament of relapsed acute myeloid leukemia. Hematol Am Soc Hematol Educ Program. 2012;2012:43–8.Google Scholar
- 7.Gallogly MM, Lazarus HM. Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016;7:73–83.Google Scholar
- 9.Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002;100(13):4372–80.CrossRefGoogle Scholar
- 10.Fathi AT, Chen YB. Treatment of FLT3-ITD acute myeloid leukemia. Am J Blood Res. 2011;1(2):175–89.Google Scholar
- 16.FDA. RYDAPT® (midostaurin): highlights of prescribing information. 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997s000lbl.pdf. Accessed Oct 2017.
- 17.Woods B, Sideris E, Palmer S, Latimer N. Nice DSU Technical Support Document 19: Partitioned survival analysis for decision modelling in health care: a critical review. 2017. Available at: http://scharr.dept.shef.ac.uk/nicedsu/wp-content/uploads/sites/7/2017/06/Partitioned-Survival-Analysis-final-report.pdf. Accessed Sep 2017.
- 20.Cheng MJ, Hourigan CS, Smith TJ. Adult acute myeloid leukemia long-term survivors. J Leuk (Los Angel). 2014;2(2):1–15 (pii: 26855).Google Scholar
- 21.Arias E. United States life tables, 2010. Natl Vital Stat Rep. 2014;63(7):1–63.Google Scholar
- 24.National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology for acute myeloid leukemia, V.1.2017. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed Mar 2017.
- 25.Truven Health Analytics. RED BOOK Online. 2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/. Accessed Sep 2017.
- 26.Centers for Medicare & Medicaid Services. Physician Fee Schedule. Available at: https://www.cms.gov/apps/physician-fee-schedule/overview.aspx. Accessed May 2016.
- 27.Centers for Medicare & Medicaid Services. Clinical Laboratory Fee Schedule. 2016. Available at: https://www.cms.gov/medicare/medicare-fee-for-service-payment/clinicallabfeesched/clinlab.html. Accessed May 2016.
- 28.Agency for Healthcare Research and Quality. HCUP. Nationwide Inpatient Sample (NIS). 2013. Available at: http://hcupnet.ahrq.gov/. Accessed 26 May 2016.
- 30.Bureau of Labor Statistics. Consumer Price Index Medical Care Component. Available at: http://data.bls.gov/pdq/SurveyOutputServlet. Accessed Sep 2016.
- 31.Joshi N, Hensen M, Patel S, Xu W, Lasch K, Stolk E. Health state utilities for acute myeloid leukaemia: a time trade-off study. Pharmacoeconomics. https://doi.org/10.1007/s40273-018-0704-8 (epub 23 Aug 2018).
- 32.Institute for Clinical and Economic Review. Overview of the ICER value assessment framework and update for 2017–2019. Available at: https://icer-review.org/wp-content/uploads/2017/06/ICER-value-assessment-framework-update-FINAL-062217.pdf. Accessed 22 June 2017.
- 34.Bae YH, Mullins CD. Do value thresholds for oncology drugs differ from nononcology drugs? J Manag Care Spec Pharm. 2014;20(11):1086–92.Google Scholar
- 35.Institute for Clinical and Economic Review (ICER). Final value assessment framework for 2017–2019. 2017. Available at: https://icer-review.org/final-vaf-2017-2019/. Accessed Sep 2017.