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Ponatinib and palbociclib combination in TKI-resistant CML—A case report

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Summary

Background

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by BCR-ABL1-derived permanent proliferation of myeloid progenitor cells. BCR-ABL1 tyrosine kinase inhibitors (TKI) are effective first-line therapeutic options to suppress tumor proliferation. However, TKI therapy is not always curative and drug-related side effects as well as drug resistance may evolve over time, necessitating salvage therapies.

Methods

In this case report we present a 68-year-old woman who developed second- and third-generation TKI therapy resistance with BCR-ABL1T315I and BCR-ABL1E255V mutation. Considering contraindication for hematopoietic stem cell transplantation, we treated the patient in an individual treatment attempt with a third-generation TKI ponatinib in combination with palbociclib, a CDK4/CDK6 inhibitor, which has been shown to effectively inhibit proliferation of BCR-ABL1T315I-mutated cells in vitro.

Results

Our case study shows strong antineoplastic effects using this combination in an advanced CML patient resistant to ponatinib monotherapy as a fourth-line treatment. Combined administration of ponatinib/palbociclib at full dose showed almost a tenfold decrease (42.6 to 4.4 IS%) of BCR-ABL1-positive cells but with simultaneous hematopoietic toxicity, necessitating dose reduction.

Conclusion

This combination treatment showed high clinical activity. However, biological activity needs to be further characterized in prospective clinical trials.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, Haematology and Medical Oncology, LKH Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria

    Johannes B. Jaeger, Thomas Jaeger, Thomas Winder & Bernd Lorenz Hartmann

  2. St. Anna Children’s Cancer Research Institute, Zimmermannplatz 8, 1090, Vienna, Austria

    Sandra Preuner, Petra Pusic, Isabella Sponseiler & Thomas Lion

  3. Department of Pediatrics, Medical University Vienna, Vienna, Austria

    Thomas Lion

Authors
  1. Johannes B. Jaeger
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  2. Thomas Jaeger
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  3. Sandra Preuner
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  4. Petra Pusic
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  5. Isabella Sponseiler
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  6. Thomas Lion
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  7. Thomas Winder
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  8. Bernd Lorenz Hartmann
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Johannes B. Jaeger, Thomas Jaeger, Bernd Lorenz Hartmann and Thomas Winder. The first draft of the manuscript was written by Johannes B. Jaeger and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bernd Lorenz Hartmann.

Ethics declarations

Conflict of interest

T. Lion has received research funding and/or honoraria from Incyte, Ariad, Angelini, Novartis, Pfizer, Amgen and Bristol Meyers Squibb. J.B. Jaeger, T. Jaeger, S. Preuner, P. Pusic, I. Sponseiler, T. Winder and B.L. Hartmann declare that they have no competing interests.

Ethical standards

The patient was treated in accordance with the Austrian law of “individual healing attempt”. No ethics approval is required under this law. Detailed information was provided to the patient and patient consent was obtained. Informed consent obtained from patient to participate. Informed consent obtained from patient for publication of this report.

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Jaeger, J.B., Jaeger, T., Preuner, S. et al. Ponatinib and palbociclib combination in TKI-resistant CML—A case report. memo 14, 402–405 (2021). https://doi.org/10.1007/s12254-021-00742-0

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  • DOI: https://doi.org/10.1007/s12254-021-00742-0

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