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Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate.
Clin Cancer Res 2005; 11(9):3425-32CC

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-alpha 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.

Authors+Show Affiliations

Departments of Leukemia, the University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. jcortes@mdanderson.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

15867244

Citation

Cortes, Jorge, et al. "Molecular Responses in Patients With Chronic Myelogenous Leukemia in Chronic Phase Treated With Imatinib Mesylate." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 9, 2005, pp. 3425-32.
Cortes J, Talpaz M, O'Brien S, et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005;11(9):3425-32.
Cortes, J., Talpaz, M., O'Brien, S., Jones, D., Luthra, R., Shan, J., ... Kantarjian, H. (2005). Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(9), pp. 3425-32.
Cortes J, et al. Molecular Responses in Patients With Chronic Myelogenous Leukemia in Chronic Phase Treated With Imatinib Mesylate. Clin Cancer Res. 2005 May 1;11(9):3425-32. PubMed PMID: 15867244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. 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, PY - 2005/5/4/pubmed PY - 2005/8/2/medline PY - 2005/5/4/entrez SP - 3425 EP - 32 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 11 IS - 9 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-alpha 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15867244/Molecular_responses_in_patients_with_chronic_myelogenous_leukemia_in_chronic_phase_treated_with_imatinib_mesylate_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=15867244 DB - PRIME DP - Unbound Medicine ER -