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
. 2011 Jan 15;117(2):327-35.
doi: 10.1002/cncr.25604. Epub 2010 Sep 15.

Current event-free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Aref Al-Kali  1 , Hagop Kantarjian, Jianqin Shan, Roland Bassett, Alfonso Quintás-Cardama, Gautam Borthakur, Elias Jabbour, Srdan Verstovsek, Susan O'Brien, Jorge Cortes
Affiliations

Current event-free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Aref Al-Kali et al. Cancer. .

Abstract

Background: Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second-generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event-free survival (EFS).

Methods: In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front-line therapy (n = 281) or after failure on interferon-α (IFN-α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs.

Results: For patients who received imatinib after failing on IFN-α, the 7-year EFS rate was 61%, whereas the CEFS rate was 69%. The 7-year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7-year CEFS rate of 88%.

Conclusions: CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

Dr. Cortes received research support from Novartis, Bristol-Myers Squibb, and Wyeth. Dr. Kantarjian received research support from Novartis and Bristol-Myers Squibb.

Figures

Figure 1
Figure 1
An algorithm for patients who received imatinib after failure on interferon-α failure is shown. CCyR indicates complete cytogenetic response; IM, imatinib; TKI, tyrosine kinase inhibitor; Rx, therapy; CR, complete response. Black boxes indicate events; a dagger indicates that, of 14 nonevents, 10 patients were lost to follow-up, 3 patients developed toxicity, and 1 patient developed other disease; an asterisk indicates the 4 patients categorized with “other diseases” had uterine cancer, pancreatic cancer, esophageal cancer, and myelodysplastic syndromes; a double dagger indicates that, of the 5 patients who maintained CCyR, 3 patients received dasatinib, 1 patient received bosutinib, and 1 patient received bafetinib (formerly known as INNO406); a section sign indicates that, of the 22 patients who received a second TKI, 6 patients received nilotinib, 11 patients received dasatinib, and 5 patients received bosutinib.
Figure 2
Figure 2
Event-free survival (EFS) and current EFS (CEFS) are illustrated for the patients who received imatinib after failure on interferon-α.
Figure 3
Figure 3
This is an algorithm for the patients who received imatinib as initial therapy. CCyR indicates complete cytogenetic response; IM, imatinib; FU, follow-up; TKI, tyrosine kinase inhibitor. Black boxes indicate events; a dagger indicates that 9 patients were lost to FU, 3 patients developed toxicity, and 3 patients were noncompliant; and an asterisk indicates that 1 patient developed acute myeloid leukemia, 2 patients required no further therapy, and 1 patient developed renal cell carcinoma.
Figure 4
Figure 4
Event-free survival (EFS) and current EFS (CEFS) are illustrated for the patients who received imatinib as their initial therapy.
See this image and copyright information in PMC

Comment in

References

    1. Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341:164–172. - PubMed
    1. Horner MJ, Ries LAG, Krapcho M, et al., editors. SEER Cancer Statistics Review, 1975–2006. Bethesda, Md: National Cancer Institute; [Accessed April 2010]. Based on November 2008 SEER data submission; posted to the SEER website 2009: http://seer.cancer.gov/csr/1975_2006.
    1. Putle D, Gondos A, Redaniel T, Brenner H. Survival of patients with chronic myelocytic leukemia: comparisons of estimates from clinical trial settings and population-based cancer registration [abstract] Blood (ASH Annual Meeting Abstracts) 2009;114:Abstract 899. - PMC - PubMed
    1. Guilhot F, Chastang C, Michallet M, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med. 1997;337:223–229. - PubMed
    1. Bonifazi F, de Vivo A, Rosti G, et al. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders. Blood. 2001;98:3074–3081. - PubMed