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Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study

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Abstract

The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR. Adverse events were more frequent with high-dose imatinib. Patients with ≤1 treatment interruption (vs >1) and those able to maintain imatinib ≥600 mg/day (vs <600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with long-term clinical outcomes.

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Acknowledgments

This work was supported by research funding from Novartis Pharmaceuticals Corporation. We thank Erinn Goldman, Ph.D. (ArticulateScience, LLC), for medical editorial assistance with this manuscript. We would also like to thank all investigators and patients who participated in the TOPS trial.

Conflict of interest

Dr. Baccarani acted as a consultant for Novartis and Bristol-Myers Squibb Company, Pfizer, and Ariad. Dr. Druker is a principal investigator on Novartis and Bristol-Myers Squibb clinical trials. His institution receives payment from these companies to cover patient costs, nurse/data manager salaries, and institutional overhead. He does not receive salary, and his laboratory does not receive funds. Dr. Branford received honoraria from Novartis and Bristol-Myers Squibb. Dr. Kim received research funding, honoraria and acted as a consultant for Novartis, Wyeth, and Bristol-Myers Squibb, received honoraria for Ilyang, and is a clinical trial lead for Pfizer. Dr. Pane has nothing to disclose. Dr. Mongay, Dr. Mone, and Christine-Elke Ortmann are Novartis employees and Dr. Mone holds Novartis stock. Dr. Kantarjian has nothing to disclose. Dr. Hughes received research funding/honoraria from Novartis and Bristol-Myers Squibb and consultancy from Ariad. Dr. Cortes received research funding and acted as a consultant for Bristol-Myers Squibb, Novartis, BMS, and Pfizer. Dr. Guilhot received research funding/honoraria from Novartis.

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Authors and Affiliations

  1. Department of Hematology and Oncology “L. e A. Seràgnoli,” S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy

    Michele Baccarani

  2. Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

    Brian J. Druker

  3. Centre for Cancer Biology, SA Pathology, University of Adelaide, Adelaide, Australia

    Susan Branford

  4. Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

    Dong-Wook Kim

  5. University of Naples Federico II, Naples, Italy

    Fabrizio Pane

  6. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Lidia Mongay & Manisha Mone

  7. Novartis Pharma AG, Basel, Switzerland

    Christine-Elke Ortmann

  8. The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Hagop M. Kantarjian & Jorge E. Cortes

  9. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Jerald P. Radich

  10. Division of Haematology and Centre for Cancer Biology, SA Pathology, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia

    Timothy P. Hughes

  11. Inserm CIC 1402, CHU de Poitiers, Poitiers, France

    François Guilhot

Authors
  1. Michele Baccarani
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  2. Brian J. Druker
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  3. Susan Branford
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  4. Dong-Wook Kim
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  5. Fabrizio Pane
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  6. Lidia Mongay
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  7. Manisha Mone
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  8. Christine-Elke Ortmann
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  9. Hagop M. Kantarjian
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  10. Jerald P. Radich
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  11. Timothy P. Hughes
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  12. Jorge E. Cortes
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  13. François Guilhot
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On behalf of the TOPS investigators

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Correspondence to Michele Baccarani.

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Baccarani, M., Druker, B.J., Branford, S. et al. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study. Int J Hematol 99, 616–624 (2014). https://doi.org/10.1007/s12185-014-1566-2

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  • DOI: https://doi.org/10.1007/s12185-014-1566-2

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