Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 12, pp 1985–1993

Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study


    • Abteilung Hämatologie/OnkologieUniversitätsklinikum Jena
  • Philipp D. le Coutre
    • Charité-Universitätsmedizin Berlin
  • Hagop M. Kantarjian
    • University of Texas MD Anderson Cancer Center
  • Michele Baccarani
    • University of Bologna
  • Philipp Erben
    • Universitätsmedizin Mannheim
  • Andreas Reiter
    • Universitätsmedizin Mannheim
  • Tracey McCulloch
    • Novartis Pharmaceuticals Corporation
  • Xiaolin Fan
    • Novartis Pharmaceuticals Corporation
  • Steven Novick
    • Novartis Pharmaceuticals Corporation
  • Francis J. Giles
    • Robert H Lurie Comprehensive Cancer Center of Northwestern University
Original Paper

DOI: 10.1007/s00432-013-1529-7

Cite this article as:
Hochhaus, A., le Coutre, P.D., Kantarjian, H.M. et al. J Cancer Res Clin Oncol (2013) 139: 1985. doi:10.1007/s00432-013-1529-7



Hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) are characterized by sustained overproduction of eosinophils and organ dysfunction. CEL involves the presence of clonal genetic markers, such as a fusion of FIP1-like 1 protein and platelet-derived growth factor receptor α (FIP1L1-PDGFRα, or F/P) or PDGFRα-activating mutations.


Sixteen patients with HES/CEL were enrolled in the phase 2 nilotinib registration trial (NCT00109707) and treated with nilotinib 400 mg twice daily. The median duration of treatment was 95 days (range 3–1,079).


Twelve patients had HES: 1 achieved a complete hematologic response (CHR), 3 achieved stable disease, 3 had progressive disease, and 5 were not evaluable for response. Four patients had CEL: 2 with the F/P fusion and 2 with PDGFRα-activating mutations. Both patients with an F/P fusion achieved a CHR; 1 also achieved a complete molecular response (CMR). Of the 2 patients with PDGFRα-activating mutations, 1 had stable disease and the other achieved CMR. At 24 months, overall survival in the HES group was 75.0 % (95 % CI 50.5–100.0) and no patients in the CEL group died. Median survival was not yet reached after a median follow-up of 32 months. The most common grade 3/4 hematologic laboratory abnormalities were lymphocytopenia (31.3 %) and neutropenia (25.0 %). The most common drug-related nonhematologic grade 3/4 adverse event was pruritus, which occurred in 2 patients (12.5 %).


Nilotinib 400 mg twice daily was effective in some patients with HES/CEL regardless of F/P mutation status, and the safety profile was consistent with other nilotinib studies.


NilotinibHypereosinophilic syndromeChronic eosinophilic leukemia

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© Springer-Verlag Berlin Heidelberg 2013