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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

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Abstract

Purpose

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.

Methods

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).

Results

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 %).

Conclusions

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.

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Acknowledgment

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. The authors thank Erinn Goldman, PhD, and Pamela Tuttle, PhD, for medical editorial assistance with this manuscript.

Conflict of interest

AH received research funding from Novartis Pharmaceuticals Corporation. PDlC received research funding from Novartis and honoraria as a speaker from Novartis, Bristol-Myers Squibb (BMS), Pfizer, and ARIAD Pharmaceuticals. HMK received research funding from Novartis Pharmaceuticals Corporation, Pfizer, ARIAD Pharmaceuticals, and BMS. MB acted as a consultant, received honoraria and attended a speakers’ bureau for Novartis Pharmaceuticals Corporation, BMS, and Pfizer. PE has no financial conflicts to disclose. AR acted as a consultant and received honoraria from Novartis Pharmaceuticals Corporation. TM and XF are employees of Novartis Pharmaceuticals Corporation. SN is an employee and stockholder of Novartis Pharmaceuticals Corporation. FJG acted as a consultant and received research funding from Novartis Pharmaceuticals Corporation.

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Authors and Affiliations

  1. Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany

    Andreas Hochhaus

  2. Charité-Universitätsmedizin Berlin, Berlin, Germany

    Philipp D. le Coutre

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

    Hagop M. Kantarjian

  4. University of Bologna, Bologna, Italy

    Michele Baccarani

  5. Universitätsmedizin Mannheim, Mannheim, Germany

    Philipp Erben & Andreas Reiter

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

    Tracey McCulloch, Xiaolin Fan & Steven Novick

  7. Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

    Francis J. Giles

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  1. Andreas Hochhaus
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  2. Philipp D. le Coutre
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Correspondence to Andreas Hochhaus.

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Hochhaus, A., le Coutre, P.D., Kantarjian, H.M. et al. 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. J Cancer Res Clin Oncol 139, 1985–1993 (2013). https://doi.org/10.1007/s00432-013-1529-7

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