Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2012 Dec 10;30(35):4323-9.
doi: 10.1200/JCO.2011.40.5217. Epub 2012 Oct 29.

Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib

Susan Branford  1 , Dong-Wook Kim, Simona Soverini, Ariful Haque, Yaping Shou, Richard C Woodman, Hagop M Kantarjian, Giovanni Martinelli, Jerald P Radich, Giuseppe Saglio, Andreas Hochhaus, Timothy P Hughes, Martin C Müller
Affiliations
Clinical Trial

Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib

Susan Branford et al. J Clin Oncol. .

Abstract

Purpose: The association between initial molecular response and longer-term outcomes with nilotinib was examined.

Patients and methods: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237).

Results: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%.

Conclusion: Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.

Trial registration: ClinicalTrials.gov NCT00471497.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram of patients included in the analysis. CCyR, complete cytogenetic response; EFS, event-free survival; MCyR, major cytogenetic response; MMR, major molecular response; PCR, polymerase chain reaction.
Fig 2.
Fig 2.
Cumulative incidence of complete cytogenetic response (CCyR) by BCR-ABL1 ratio at 3 months in (A) all patients, (B) imatinib-resistant patients, and (C) patients with a baseline mutation.
Fig 3.
Fig 3.
Cumulative incidence of major cytogenetic response (MCyR) by BCR-ABL1 ratio at 1 month (all patients).
Fig 4.
Fig 4.
Cumulative incidence of major molecular response (MMR) by BCR-ABL1 ratio at 3 months in (A) all patients, (B) imatinib-resistant patients, and (C) patients with a baseline mutation.
See this image and copyright information in PMC

References

    1. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129–141. - PubMed
    1. Golemovic M, Verstovsek S, Giles F, et al. AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin Cancer Res. 2005;11:4941–4947. - PubMed
    1. Manley PW, Drueckes P, Fendrich G, et al. Extended kinase profile and properties of the protein kinase inhibitor nilotinib. Biochim Biophys Acta. 2010;1804:445–453. - PubMed
    1. Kantarjian HM, Giles FJ, Bhalla KN, et al. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase following imatinib resistance or intolerance: 24-month follow-up results. Blood. 2011;117:1141–1145. - PMC - PubMed
    1. Kantarjian HM, Giles F, Gattermann N, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110:3540–3546. - PubMed

Publication types

MeSH terms

Associated data