Cost Effectiveness of the Third-Generation Tyrosine Kinase Inhibitor (TKI) Ponatinib, vs. Second-Generation TKIs or Stem Cell Transplant, as Third-Line Treatment for Chronic-Phase Chronic Myeloid Leukemia

  • Carsten Hirt
  • Sergio IannazzoEmail author
  • Silvia Chiroli
  • Lisa J. McGarry
  • Philipp le Coutre
  • Leif Stenke
  • Torsten Dahlén
  • Jeffrey H. Lipton
Original Research Article


Background and Objectives

Third-line treatment options for patients with chronic-phase chronic myeloid leukemia include tyrosine kinase inhibitors and allogeneic hematopoietic stem cell transplantation (alloHSCT). The objective of this study was to develop a Markov model with a lifetime time horizon to assess the cost effectiveness of ponatinib for third-line chronic-phase chronic myeloid leukemia vs. second-generation tyrosine kinase inhibitors (dasatinib, nilotinib, bosutinib) or alloHSCT from the public healthcare system perspective in Germany, Sweden, and Canada.


Clinical outcomes were derived from the literature, and from patient-level data (phase II PACE trial) for ponatinib. Resource use included drugs, alloHSCT, monitoring and follow-up, adverse events, and end-of-life care; costs were based on national tariffs. Quality-adjusted life-years (QALYs) were calculated using chronic myeloid leukemia health-state utilities from an international time–trade-off study. Costs and benefits were discounted at 3% per annum for Germany and Sweden, and 5% for Canada.


Ponatinib yielded more discounted QALYs than any second-generation tyrosine kinase inhibitor/alloHSCT in all three countries, mainly owing to better response rates and longer durations of response. Incremental cost-effectiveness ratios for ponatinib vs. second-generation tyrosine kinase inhibitors were US$21,543–37,755/QALY in Germany, $24,018–38,227/QALY in Sweden, and $43,001–58,515/QALY in Canada. Ponatinib was dominant over alloHSCT in Germany, while incremental cost-effectiveness ratios for ponatinib vs. alloHSCT in Sweden and Canada were $715/QALY and $31,534/QALY, respectively.


Ponatinib may improve outcomes (mainly because of higher response rates and longer response durations) at an acceptable cost level compared with other third-line treatment options for chronic-phase chronic myeloid leukemia in Germany, Sweden, and Canada; however, the lack of an indirect comparison is a limitation of our study.



The development of the models was supported by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, through a consulting contract with SIHS SRL, a company owned and directed by Sergio Iannazzo. The authors gratefully acknowledge the help of Thomas Neumann with estimating costs of alloHSCT and post-transplantation follow-up in Germany. Editorial assistance in the preparation of this manuscript was provided by W. Mark Roberts, PhD, Montreal, Canada, through a contract with Internal Market Access Consulting GmbH, and by Abigail Marmont, PhD, CMPP of Evidence Scientific Solutions, Inc. (Philadelphia, PA, USA), and was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Author Contributions

CH, SI, SC, and LJM contributed to the study conception, study design, and data analysis. PC, LS, and TD contributed to the study design. JHL contributed to the data analysis. All authors contributed to the drafting/revision of the manuscript and approved the final version.

Compliance with Ethical Standards


This study was sponsored by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Open access for this manuscript was sponsored by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Conflict of interest

Carsten Hirt has received honoraria for speaking at symposia, financial support for attending symposia, and research support from Novartis. Sergio Iannazzo has received consulting fees and research support from ARIAD Pharmaceuticals, Inc., and Incyte Biosciences Sàrl. Silvia Chiroli was an employee of Incyte when this research was conducted. Lisa J. McGarry was an employee of ARIAD when this research was conducted, and holds stocks/options in ARIAD. Philipp le Coutre has received advisory board fees and honoraria for speaking at symposia from ARIAD, Novartis, BMS, Pfizer, and Incyte, and financial support for educational programs from Novartis and BMS. Leif Stenke and Torsten Dahlén have no conflicts of interest that are directly relevant to the content of this article. Jeffrey H. Lipton has received consulting and advisory board fees and research support from ARIAD, Novartis, BMS, and Pfizer, as well as honoraria for speaking at symposia and financial support for educational programs from Novartis, BMS, and Pfizer.

Ethics approval

Patient-level data used in this study were derived from the PACE clinical trial. PACE was approved by local ethics committees and was conducted in accordance with the Declaration of Helsinki and the International Council for Harmonization guidelines for good clinical practice. All patients provided written informed consent.

Data availability

All data generated or analyzed during this study are included in this published article.

Supplementary material

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Internal Medicine C, Hematology and OncologyGreifswald University Medical CenterGreifswaldGermany
  2. 2.SIHS Health Economics Consulting, SIHS SRLTurinItaly
  3. 3.Incyte Biosciences International SàrlEpalingesSwitzerland
  4. 4.ARIAD Pharmaceuticals, Inc., a Wholly Owned Subsidiary of Takeda Pharmaceutical Company LimitedCambridgeUSA
  5. 5.Charité, University of Medicine BerlinBerlinGermany
  6. 6.Division of Hematology and Department of Medicine SolnaKarolinska University Hospital and Karolinska InstitutetStockholmSweden
  7. 7.Cancer Clinical Research UnitPrincess Margaret Cancer CentreTorontoCanada
  8. 8.Prothena Switzerland GmbHZugSwitzerland
  9. 9.Vertex Pharmaceuticals Inc.BostonUSA

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