, Volume 37, Issue 2, pp 239–253 | Cite as

Cost Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States

  • Eytan Stein
  • Jipan XieEmail author
  • Emilie Duchesneau
  • Subrata Bhattacharyya
  • Umakanth Vudumula
  • Briana Ndife
  • Gaetano Bonifacio
  • Annie Guerin
  • Nanxin Li
  • George Joseph
Original Research Article



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.

Author Contributions

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.

Ethical approval

This study did not involve human participants, therefore no formal consent was required.

Data availability

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.

Supplementary material

40273_2018_732_MOESM1_ESM.pdf (417 kb)
Supplementary material 1 (PDF 417 kb)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Eytan Stein
    • 1
  • Jipan Xie
    • 2
    Email author
  • Emilie Duchesneau
    • 3
  • Subrata Bhattacharyya
    • 4
  • Umakanth Vudumula
    • 4
  • Briana Ndife
    • 5
  • Gaetano Bonifacio
    • 5
  • Annie Guerin
    • 6
  • Nanxin Li
    • 3
  • George Joseph
    • 5
  1. 1.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Analysis Group, Inc.Los AngelesUSA
  3. 3.Analysis Group, Inc.BostonUSA
  4. 4.Novartis Healthcare Private LimitedHyderabadIndia
  5. 5.Novartis Pharmaceuticals CorporationEast HanoverUSA
  6. 6.Analysis Group, Inc.MontréalCanada

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