Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase

Fabio P.S. Santos, Hagop Kantarjian, David McConkey, Susan O'Brien, Stefan Faderl, Gautam Borthakur, Alessandra Ferrajoli, John Wright, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Background: Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma (MM) and mantle-cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. Methods: We conducted a pilot trial to evaluate the activity of single-agent bortezomib in CML. Seven patients with imatinibrefractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11 every 3 weeks. Results: The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients experienced grade 3/4 nonhematologic toxicities. Conclusion: Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to using proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors (TKIs) or as a strategy to eradicate leukemic stem cells.

Original languageEnglish (US)
Pages (from-to)355-360
Number of pages6
JournalClinical Lymphoma, Myeloma and Leukemia
Volume11
Issue number4
DOIs
StatePublished - Aug 2011
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Proteasome Inhibitors
Apoptosis
Mantle-Cell Lymphoma
Basophils
Myeloid Cells
Proteasome Endopeptidase Complex
Multiple Myeloma
Cytogenetics
Protein-Tyrosine Kinases
Bortezomib
Imatinib Mesylate
Stem Cells
Therapeutics
Growth
Neoplasms

Keywords

  • Bortezomib
  • Chronic myelogenous leukemia
  • Proteasome inhibitors

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase. / Santos, Fabio P.S.; Kantarjian, Hagop; McConkey, David; O'Brien, Susan; Faderl, Stefan; Borthakur, Gautam; Ferrajoli, Alessandra; Wright, John; Cortes, Jorge.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 11, No. 4, 08.2011, p. 355-360.

Research output: Contribution to journalArticle

Santos, FPS, Kantarjian, H, McConkey, D, O'Brien, S, Faderl, S, Borthakur, G, Ferrajoli, A, Wright, J & Cortes, J 2011, 'Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase', Clinical Lymphoma, Myeloma and Leukemia, vol. 11, no. 4, pp. 355-360. https://doi.org/10.1016/j.clml.2011.06.004
Santos, Fabio P.S. ; Kantarjian, Hagop ; McConkey, David ; O'Brien, Susan ; Faderl, Stefan ; Borthakur, Gautam ; Ferrajoli, Alessandra ; Wright, John ; Cortes, Jorge. / Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase. In: Clinical Lymphoma, Myeloma and Leukemia. 2011 ; Vol. 11, No. 4. pp. 355-360.
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