Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders.

Abstract

BACKGROUND:

Imatinib mesylate is a selective tyrosine kinase inhibitor of c-abl, bcr/abl, c-kit, and platelet-derived growth factor-receptor (PDGF-R). c-kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD).

METHODS:

The authors investigated the efficacy of imatinib in patients with these disorders. Forty-eight patients with AML (n = 10), MDS (n = 8), myelofibrosis (n = 18), atypical chronic myeloid leukemia (CML; n = 7), chronic myelomonocytic leukemia (CMML; n = 3), or polycythemia vera (n = 2) were treated with imatinib 400 mg daily.

RESULTS:

None of the patients with AML or MDS responded. Among patients with myelofibrosis, 10 of 14 patients with splenomegaly (71%) had a 30% or greater reduction in spleen size, 1 patient had trilineage hematologic improvement, 2 had erythroid hematologic improvement, and 1 had improvement in platelet count. One patient with atypical CML had erythroid hematologic improvement. Both patients with polycythemia vera needed fewer phlebotomies (from 2-3 per year to none during the 8 months of therapy and from 3-6 per year to 1 during 9 months of therapy). None of the three patients with CMML responded. Treatment was well tolerated. The side effects were similar to those observed in patients with CML.

CONCLUSIONS:

Within these small subgroups of disease types, single-agent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGF-R fusion genes. Preliminary data on polycythemia vera are promising and deserve further investigation. Responses among myelofibrosis patients were minor. Therefore, a combination treatment regimen including imatinib may be more effective.

• Authors: Jorge Cortes, Francis Giles, Susan O'Brien, Deborah Thomas, Maher Albitar, Mary Beth Rios, Moshe Talpaz, Guillermo Garcia-Manero, Stefan Faderl, Laurie Letvak, August Salvado, Hagop Kantarjian
• Journal: Cancer (Cancer) Vol. 97 Issue 11 Pg. 2760-6 (Jun 01 2003) ISSN: 0008-543X [Print] United States
• PMID: 12767088 (Publication Type: Journal Article)
• Copyright: Copyright 2003 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use, toxicity)
• Benzamides
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
• Leukemia, Myeloid, Acute (drug therapy)
• Leukemia, Myelomonocytic, Chronic (drug therapy)
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Myeloproliferative Disorders (drug therapy)
• Piperazines (therapeutic use, toxicity)
• Polycythemia Vera (drug therapy)
• Primary Myelofibrosis (drug therapy)
• Pyrimidines (therapeutic use, toxicity)
• Recurrence