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Fatal progressive cerebral ischemia in CML under third-line treatment with ponatinib

Leukemia volume 28, pages 976–977 (2014)Cite this article

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The third generation tyrosine kinase inhibitor (TKI) ponatinib extends the therapeutic armamentarium for the management of nilotinib- and dasatinib-refractory chronic myeloid leukemia (CML).1 Vascular complications, especially arterial events, have been associated with nilotinib and ponatinib only and are an emerging issue when using these two TKIs in CML.2, 3, 4, 5

A 52-year-old male patient was diagnosed in June 2011 with high-risk (Hasford and Sokal score) Ph-positive CML in early chronic phase (CP) with additional trisomy 8 and monosomy 7. At diagnosis, leukocytes exceeded 400 G/l and hemoglobin was 7.9 g/dl, whereas platelets were within the normal range. The patient’s history did not show any relevant metabolic and/or vascular risk factors or comorbidities. Treatment with nilotinib (300 mg b.i.d.) was initiated within a clinical trial and the patient rapidly achieved a complete hematological response (CHR) followed by a complete cytogenetic response at month 8 (limitation of this analysis was the evaluation of 11 metaphases only). The patient never reached major molecular response, the minimum BCR-ABLIS he achieved was 7% at month 6. After 1 year of therapy BCR-ABLIS increased by 40% followed by subsequent loss of CHR with increasing leukocytes, rising up to 30 G/l (that is, treatment failure according to European LeukemiaNet (ELN)).6 BCR-ABL mutations were not detected and the patient’s compliance was not an issue. Five weeks after switching to dasatinib 100 mg/day, leukocytes remained elevated and dasatinib was subsequently escalated to 140 mg/day for 4 weeks, again without response (bone marrow smear and differential blood counts still showed CP-CML). The third generation TKI ponatinib (45 mg/day) was then initiated to further reduce leukemic burden before the planned allogeneic peripheral blood stem cell transplantation from an available 10/10 unrelated donor.

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Authors and Affiliations

  1. Medical Clinic III for Oncology, Haematology and Rheumatology, University Hospital Bonn (UKB), Bonn, Germany

    K Mayer & D Wolf

  2. Institute of Neuropathology, University Hospital Bonn (UKB), Bonn, Germany

    G H Gielen

  3. Department of Radiology, University Hospital Bonn (UKB), Bonn, Germany

    W Willinek

  4. Medical Clinic III, University Hospital Mannheim, Mannheim, Germany

    M C Müller

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  1. K Mayer
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  2. G H Gielen
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  3. W Willinek
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  4. M C Müller
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  5. D Wolf
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Correspondence to K Mayer.

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Competing interests

DW receives research support from Novartis, speaker’s honorary from BMS, Pfizer and Novartis. MCM receives research support from Novartis and BMS, and speaker’s honorary from BMS, Pfizer and Novartis. The remaining authors declare no conflict of interest.

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Mayer, K., Gielen, G., Willinek, W. et al. Fatal progressive cerebral ischemia in CML under third-line treatment with ponatinib. Leukemia 28, 976–977 (2014). https://doi.org/10.1038/leu.2013.320

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