Imatinib mesylate therapy of chronic phase chronic myeloid leukemia resistant or intolerant to interferon: results and prognostic factors for response and progression-free survival in 150 patients.

Abstract

BACKGROUND AND OBJECTIVES:

Imatinib mesylate has recently been shown to be highly effective in chronic-phase chronic myeloid leukemia (CML). The results of imatinib treatment in chronic-phase CML patients resistant or intolerant to interferon (IFN) and the factors predicting therapeutic response and progression-free survival were analyzed.

DESIGN AND METHODS:

One hundred and fifty patients with chronic-phase CML resistant (n=111) or intolerant (n=39) to IFN were treated with imatinib. Prognostic factors for response and disease progression were assessed by multivariate analysis.

RESULTS:

The median time from diagnosis was 43 months (0.5-188), median IFN therapy 21.5 months (0.5-140) and median follow-up from starting imatinib 13.6 months (range: 3-23). Complete hematologic response was achieved in 96 of 97 patients. Complete, partial and minor cytogenetic responses were present in 44%, 22%, and 8% of patients at 12 months. Grade III-IV neutropenia, thrombocytopenia, and anemia developed in 33%, 16%, and 6% of patients, respectively. Sixty-five patients discontinued treatment for a median of 4 weeks (1-36) due to toxicity. The rate of progression-free survival (lack of accelerated/blastic phase with persistent response) was 89.2% (95% CI: 84-94.4) at 12 months and 80.2% (95% CI: 72.2-88.2) at 18 months. Platelets > 450x10(9)/L and treatment discontinuation > 4 weeks were associated with a lower rate of major (complete plus partial) cytogenetic response. Patients in Sokal's high-risk group and those who did not achieve a major cytogenetic response had significantly shorter progression-free survival.

INTERPRETATION AND CONCLUSIONS:

Imatinib is highly effective in chronic-phase CML patients resistant or intolerant to IFN, especially in those with normal platelet counts and in those not requiring prolonged treatment discontinuation due to neutropenia.

• Authors: Francisco Cervantes, Juan-Carlos Hernández-Boluda, Juan-Luis Steegmann, Eulogio Conde, Alberto Alvarez-Larrán, Javier López-Jiménez, Santiago Osorio, Lucía Villalón, Mireia Camós, Javier García-Conde, Jesús Odriozola
• Journal: Haematologica (Haematologica) Vol. 88 Issue 10 Pg. 1117-22 (Oct 2003) ISSN: 1592-8721 [Electronic] Italy
• PMID: 14555307 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate
• Interferons

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Benzamides
• Disease-Free Survival
• Drug Administration Schedule
• Drug Hypersensitivity (pathology)
• Drug Resistance, Neoplasm
• Female
• Humans
• Imatinib Mesylate
• Interferons (immunology, metabolism, therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid, Chronic-Phase (drug therapy, metabolism)
• Male
• Middle Aged
• Piperazines (administration & dosage, therapeutic use, toxicity)
• Prognosis
• Pyrimidines (administration & dosage, therapeutic use, toxicity)
• Spain
• Treatment Outcome