Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate

Jorge Cortes, Moshe Talpaz, Susan O'Brien, Dan Jones, Rajyalakshmi Luthra, Jenny Shan, Francis Giles, Stefan Faderl, Srdan Verstovsek, Guillermo Garcia-Manero, Mary B. Rios, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

Purpose: To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib. Experimental Design: We analyzed the results of quantitative PCR in 280 patients with CML in chronic phase who achieved complete cytogenetic remission with imatinib (117 after IFN-α failure and 163 previously untreated). Median follow-up was 31 months (range, 3-52 months). Results: Median BCR-ABL/ABL ratio before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular response (BCR-ABL/ABL ratio <0.05%) was achieved in 174 (62%), and transcripts became undetectable (complete molecular response) in 95 (34%). By multivariate analysis, only treatment with high-dose imatinib (P = 0.02) was associated with achievement of a major molecular response. Nine of 166 (5%) patients who achieved a major molecular response lost their cytogenetic remission, compared with 25 of 68 (37%) among those who did not achieve this response (P < 0.0001). Patients achieving a major molecular response 12 months after the start of therapy had significantly better complete cytogenetic remission duration than others. A >1-log reduction in transcript levels after 3 months of therapy predicted for an improved probability of achieving a major molecular response at 24 months. Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic remission only among patients who did not achieve a major molecular response. Conclusions: Achieving a major molecular response, particularly within the first year of therapy, is predictive of a durable cytogenetic remission and may be the future goal of therapy in CML.

Original languageEnglish (US)
Pages (from-to)3425-3432
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number9
DOIs
StatePublished - May 1 2005
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Cytogenetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Therapeutics
Research Design
Recurrence
Polymerase Chain Reaction
Imatinib Mesylate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. / Cortes, Jorge; Talpaz, Moshe; O'Brien, Susan; Jones, Dan; Luthra, Rajyalakshmi; Shan, Jenny; Giles, Francis; Faderl, Stefan; Verstovsek, Srdan; Garcia-Manero, Guillermo; Rios, Mary B.; Kantarjian, Hagop.

In: Clinical Cancer Research, Vol. 11, No. 9, 01.05.2005, p. 3425-3432.

Research output: Contribution to journalArticle

Cortes, J, Talpaz, M, O'Brien, S, Jones, D, Luthra, R, Shan, J, Giles, F, Faderl, S, Verstovsek, S, Garcia-Manero, G, Rios, MB & Kantarjian, H 2005, 'Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate', Clinical Cancer Research, vol. 11, no. 9, pp. 3425-3432. https://doi.org/10.1158/1078-0432.CCR-04-2139
Cortes, Jorge ; Talpaz, Moshe ; O'Brien, Susan ; Jones, Dan ; Luthra, Rajyalakshmi ; Shan, Jenny ; Giles, Francis ; Faderl, Stefan ; Verstovsek, Srdan ; Garcia-Manero, Guillermo ; Rios, Mary B. ; Kantarjian, Hagop. / Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 9. pp. 3425-3432.
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abstract = "Purpose: To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib. Experimental Design: We analyzed the results of quantitative PCR in 280 patients with CML in chronic phase who achieved complete cytogenetic remission with imatinib (117 after IFN-α failure and 163 previously untreated). Median follow-up was 31 months (range, 3-52 months). Results: Median BCR-ABL/ABL ratio before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular response (BCR-ABL/ABL ratio <0.05{\%}) was achieved in 174 (62{\%}), and transcripts became undetectable (complete molecular response) in 95 (34{\%}). By multivariate analysis, only treatment with high-dose imatinib (P = 0.02) was associated with achievement of a major molecular response. Nine of 166 (5{\%}) patients who achieved a major molecular response lost their cytogenetic remission, compared with 25 of 68 (37{\%}) among those who did not achieve this response (P < 0.0001). Patients achieving a major molecular response 12 months after the start of therapy had significantly better complete cytogenetic remission duration than others. A >1-log reduction in transcript levels after 3 months of therapy predicted for an improved probability of achieving a major molecular response at 24 months. Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic remission only among patients who did not achieve a major molecular response. Conclusions: Achieving a major molecular response, particularly within the first year of therapy, is predictive of a durable cytogenetic remission and may be the future goal of therapy in CML.",
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AU - Cortes, Jorge

AU - Talpaz, Moshe

AU - O'Brien, Susan

AU - Jones, Dan

AU - Luthra, Rajyalakshmi

AU - Shan, Jenny

AU - Giles, Francis

AU - Faderl, Stefan

AU - Verstovsek, Srdan

AU - Garcia-Manero, Guillermo

AU - Rios, Mary B.

AU - Kantarjian, Hagop

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N2 - Purpose: To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib. Experimental Design: We analyzed the results of quantitative PCR in 280 patients with CML in chronic phase who achieved complete cytogenetic remission with imatinib (117 after IFN-α failure and 163 previously untreated). Median follow-up was 31 months (range, 3-52 months). Results: Median BCR-ABL/ABL ratio before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular response (BCR-ABL/ABL ratio <0.05%) was achieved in 174 (62%), and transcripts became undetectable (complete molecular response) in 95 (34%). By multivariate analysis, only treatment with high-dose imatinib (P = 0.02) was associated with achievement of a major molecular response. Nine of 166 (5%) patients who achieved a major molecular response lost their cytogenetic remission, compared with 25 of 68 (37%) among those who did not achieve this response (P < 0.0001). Patients achieving a major molecular response 12 months after the start of therapy had significantly better complete cytogenetic remission duration than others. A >1-log reduction in transcript levels after 3 months of therapy predicted for an improved probability of achieving a major molecular response at 24 months. Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic remission only among patients who did not achieve a major molecular response. Conclusions: Achieving a major molecular response, particularly within the first year of therapy, is predictive of a durable cytogenetic remission and may be the future goal of therapy in CML.

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