Treatment of Hypereosinophilic Syndrome (HES) with Imatinib Mesylate

Reviewer: Tracy d'Entremont, MD
OncoLink
Last Modified: December 9, 2002

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Presenter: Jorge E. Cortes
Presenter's Affiliation: M.D. Anderson Cancer Center; Houston, TX
Type of Session: Scientific

Background

  • HES is a rare hematologic disorder characterized by persistent eosinophilia associated with organ involvement.
  • The diseasae is very heterogenous but, patients tend to have a poor prognosis.
  • Treatment for HES has included steroids and chemotherapeutic agents such as: cyclophosphamide, vincristine, hydroxyurea, and interferon-alpha(IFN).
  • Imatinib is a specific tyrosine kinase inhibitor against c-abl, bcr-abl, c-kit, and PDGF-R.
  • Eosinophils express c-kit receptor and activation of this receptor leads to eosinophil proliferation.
  • For these reasons this study was performed to investigate the efficacy of imatinib in patients with HES.

Materials and Methods

  • This was a phase II study of HES patients.
  • Patients were initially treated with 100mg of imatinib daily.
  • If no response was seen after 4 weeks, the dose was escalated to 400mg/day.
  • 9 patients have been enrolled to date (6 males and 3 females) all with end-organ involvement (CNS, skin, or cardiac)

Results

  • There have been 4 CR (44%)--all males
  • There has been one transient response in a female
  • There was one early discontinuation for exacerbation of psoriasis.
  • There has been one death after 9 weeks of treatment from pneumococcal sepsis in a patient who had had prior splenectomy.
  • Other adverse events were mild with only 2 patients experiencing grade 3 toxicities.
    1 with grade 3 rash
    1 with grade 3 abdominal cramps and nausea
  • Other toxicities were mild grade 1 and included edema, diarrhea, muscle cramps and nausea.

Author's Conclusions

    Imatinib at low dose is efficacious for HES especially in male patients.

Clinical/Scientific Implications

    HES is a rare disorder with few effective therapeutic oiptions. This small phase II single institution study is intriguing and may provide a therapeutic option for a select group of HES patients. Though the data are encouraging, the numbers are very small and more patients are required before clinical practice will change.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.



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