Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia

Yesid Alvarado, Jorge Cortes, Srdan Verstovsek, Deborah Thomas, Stephan Faderl, Zeev Estrov, Hagop Kantarjian, Francis J. Giles

Research output: Contribution to journalArticle

Abstract

Purpose: Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semi-synthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducted a pilot study of Peg-IFN2b in patients with ET. Patients and methods: Patients with a history of persistent (greater than 2 months) platelet counts > 600× 109/l, with hyperplasia of bone marrow megakaryocytes in the absence of an alternate identifiable cause of thrombocytosis were eligible. Patients were required to have either thrombohemorrhagic signs and/or symptoms if previously untreated; persistence of thrombohemorrhagic signs and/or symptoms if receiving anagrelide, IFN-alpha, or hydroxyurea; or intolerance to anagrelide, IFN-alpha, or hydroxyurea. The initial PEG-IFN2b dose was from 1.5 to 4.5 μg/kg per week subcutaneously with subsequent dose adjustments as indicated by response and adverse events. Results: Eleven patients (nine female, median age 54 years, range 26-69 years) were treated. PEG-IFN2b rapidly controlled platelet counts and resolved symptoms in all patients. The median duration of PEG-IFN2b therapy on-study was 9 months (range 4-17 months). No patient had signs or symptoms of thrombosis or hemorrhage while on study. After 2 months of therapy, 10 patients (91%) were in complete remission, and 11 (100%) after 4 months. One patient discontinued therapy at 4 months because of persistent grade 3 fatigue and a second at 5 months because of anxiety and depression. Conclusion: PEG-IFN2b has significant activity in patients with ET. Long-term follow-up of a larger cohort of patients is needed to define its role in this disease.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume51
Issue number1
DOIs
StatePublished - Jan 16 2003
Externally publishedYes

Fingerprint

Essential Thrombocythemia
interferon alfa-2b
Polymers
Platelets
Interferon-alpha
Hydroxyurea
Bone
Platelet Count
Signs and Symptoms
Megakaryocytes
peginterferon alfa-2b
Fatigue of materials
Bone Marrow
Social Adjustment
Thrombocytosis
Proteins
Hyperplasia
Fatigue
Half-Life
Thrombosis

Keywords

  • Efficacy
  • Essential thrombocythemia
  • Pegylated interferon

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia. / Alvarado, Yesid; Cortes, Jorge; Verstovsek, Srdan; Thomas, Deborah; Faderl, Stephan; Estrov, Zeev; Kantarjian, Hagop; Giles, Francis J.

In: Cancer Chemotherapy and Pharmacology, Vol. 51, No. 1, 16.01.2003, p. 81-86.

Research output: Contribution to journalArticle

Alvarado, Y, Cortes, J, Verstovsek, S, Thomas, D, Faderl, S, Estrov, Z, Kantarjian, H & Giles, FJ 2003, 'Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia', Cancer Chemotherapy and Pharmacology, vol. 51, no. 1, pp. 81-86. https://doi.org/10.1007/s00280-002-0533-4
Alvarado, Yesid ; Cortes, Jorge ; Verstovsek, Srdan ; Thomas, Deborah ; Faderl, Stephan ; Estrov, Zeev ; Kantarjian, Hagop ; Giles, Francis J. / Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia. In: Cancer Chemotherapy and Pharmacology. 2003 ; Vol. 51, No. 1. pp. 81-86.
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AU - Cortes, Jorge

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AU - Faderl, Stephan

AU - Estrov, Zeev

AU - Kantarjian, Hagop

AU - Giles, Francis J.

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AB - Purpose: Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semi-synthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducted a pilot study of Peg-IFN2b in patients with ET. Patients and methods: Patients with a history of persistent (greater than 2 months) platelet counts > 600× 109/l, with hyperplasia of bone marrow megakaryocytes in the absence of an alternate identifiable cause of thrombocytosis were eligible. Patients were required to have either thrombohemorrhagic signs and/or symptoms if previously untreated; persistence of thrombohemorrhagic signs and/or symptoms if receiving anagrelide, IFN-alpha, or hydroxyurea; or intolerance to anagrelide, IFN-alpha, or hydroxyurea. The initial PEG-IFN2b dose was from 1.5 to 4.5 μg/kg per week subcutaneously with subsequent dose adjustments as indicated by response and adverse events. Results: Eleven patients (nine female, median age 54 years, range 26-69 years) were treated. PEG-IFN2b rapidly controlled platelet counts and resolved symptoms in all patients. The median duration of PEG-IFN2b therapy on-study was 9 months (range 4-17 months). No patient had signs or symptoms of thrombosis or hemorrhage while on study. After 2 months of therapy, 10 patients (91%) were in complete remission, and 11 (100%) after 4 months. One patient discontinued therapy at 4 months because of persistent grade 3 fatigue and a second at 5 months because of anxiety and depression. Conclusion: PEG-IFN2b has significant activity in patients with ET. Long-term follow-up of a larger cohort of patients is needed to define its role in this disease.

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