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Erschienen in: memo - Magazine of European Medical Oncology 4/2021

20.09.2021 | case report

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

verfasst von: Johannes B. Jaeger, Thomas Jaeger, Sandra Preuner, Petra Pusic, Isabella Sponseiler, Thomas Lion, Thomas Winder, Bernd Lorenz Hartmann

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 4/2021

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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.
Literatur
1.
Zurück zum Zitat Khorashad JS, Kelley TW, Szankasi P, Mason CC, Soverini S, Adrian LT, et al. BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: Frequency and clonal relationships. Blood. 2013;121(3):489–98. CrossRef Khorashad JS, Kelley TW, Szankasi P, Mason CC, Soverini S, Adrian LT, et al. BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: Frequency and clonal relationships. Blood. 2013;121(3):489–98. CrossRef
5.
Zurück zum Zitat Miller GD, Bruno BJ, Lim CS. Resistant mutations in CML and Ph+ALL—role of ponatinib. Biol Targets Ther. 2014;8:243–54. Miller GD, Bruno BJ, Lim CS. Resistant mutations in CML and Ph+ALL—role of ponatinib. Biol Targets Ther. 2014;8:243–54.
Metadaten
Titel
Ponatinib and palbociclib combination in TKI-resistant CML—A case report
verfasst von
Johannes B. Jaeger
Thomas Jaeger
Sandra Preuner
Petra Pusic
Isabella Sponseiler
Thomas Lion
Thomas Winder
Bernd Lorenz Hartmann
Publikationsdatum
20.09.2021
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 4/2021
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-021-00742-0