Imatinib mesylate in the treatment of systemic mastocytosis

A phase II trial

Authors

  • Helga J. Droogendijk MD,

    1. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
    2. Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands
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  • Hanneke J. C. Kluin-Nelemans MD,

    1. Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands
    2. Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands
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  • Jaap J. van Doormaal MD,

    1. Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands
    2. Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands
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  • Arnold P. Oranje MD,

    1. Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands
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  • Arjan A. van de Loosdrecht MD,

    1. Department of Hematology, Vrije Universiteit University Medical Center, Amsterdam, the Netherlands
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  • Paul L. A. van Daele MD, PhD

    Corresponding author
    1. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
    2. Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands
    • Department of Internal Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
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    • Fax: (011) 31 10463 3268


Abstract

BACKGROUND.

Mastocytosis is characterized by the abnormal proliferation of mast cells in 1 or more organs. In most patients, a mutation is present in the gene for C-KIT, resulting in deregulation of the c-kit receptor. Imatinib mesylate is a potent inhibitor of c-kit receptor tyrosine kinase activity. Therefore, the authors evaluated the efficacy and safety of imatinib mesylate as treatment for patients with systemic mastocytosis.

METHODS.

Patients with systemic mastocytosis received imatinib mesylate orally at a dose of 400 mg once daily for 3 to 6 months. Low doses of prednisone were added during the first 2 weeks. Endpoints were reductions in serum tryptase, urinary N-methylhistamine excretion, skin lesions, the number of mast cells in bone marrow sections, hepatomegaly and/or splenomegaly, and symptoms.

RESULTS.

Of 14 patients who were included in the study, 11 patients had the D816V mutation. One patient expressed the FIP1L1-PDGFR-α rearrangement gene. In 2 patients, no mutation was found. In 10 patients, serum tryptase levels decreased >20%. In all patients, urinary N-methylhistamine excretion was reduced. In 8 of 13 evaluable patients, the number of mast cells in the bone marrow decreased. Skin symptoms diminished in 5 of 9 patients. Hepatosplenomegaly improved in 3 of 6 patients. Symptoms decreased in 8 of 13 patients. In all patients who had the D816V mutation, reductions in ≥2 endpoints were achieved. In the patient who expressed the FIP1L1-PDGFR-α rearrangement gene, a complete response was attained. In general, imatinib mesylate was tolerated well.

CONCLUSIONS.

Imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation. Cancer 2006. © 2006 American Cancer Society.

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