Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: An analysis from the International Randomized Study of Interferon and STI571 (IRIS)

Timothy P. Hughes, Andreas Hochhaus, Susan Branford, Martin C. Müller, Jaspal S. Kaeda, Letizia Foroni, Brian Druker, François Guilhot, Richard A. Larson, Stephen G. O'Brien, Marc S. Rudoltz, Manisha Mone, Elisabeth Wehrle, Vijay Modur, John M. Goldman, Jerald P. Radich

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Abstract

This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases inBCR-ABL transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) ≤ 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (P <.001). This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at www.clinicaltrials.gov as NCT00006343.

Original languageEnglish (US)
Pages (from-to)3758-3765
Number of pages8
JournalBlood
Volume116
Issue number19
DOIs
StatePublished - Nov 11 2010

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferons
Blast Crisis
Disease-Free Survival
Cytogenetics
Survival Rate
Imatinib Mesylate
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia : An analysis from the International Randomized Study of Interferon and STI571 (IRIS). / Hughes, Timothy P.; Hochhaus, Andreas; Branford, Susan; Müller, Martin C.; Kaeda, Jaspal S.; Foroni, Letizia; Druker, Brian; Guilhot, François; Larson, Richard A.; O'Brien, Stephen G.; Rudoltz, Marc S.; Mone, Manisha; Wehrle, Elisabeth; Modur, Vijay; Goldman, John M.; Radich, Jerald P.

In: Blood, Vol. 116, No. 19, 11.11.2010, p. 3758-3765.

Research output: Contribution to journalArticle

Hughes, TP, Hochhaus, A, Branford, S, Müller, MC, Kaeda, JS, Foroni, L, Druker, B, Guilhot, F, Larson, RA, O'Brien, SG, Rudoltz, MS, Mone, M, Wehrle, E, Modur, V, Goldman, JM & Radich, JP 2010, 'Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: An analysis from the International Randomized Study of Interferon and STI571 (IRIS)', Blood, vol. 116, no. 19, pp. 3758-3765. https://doi.org/10.1182/blood-2010-03-273979
Hughes, Timothy P. ; Hochhaus, Andreas ; Branford, Susan ; Müller, Martin C. ; Kaeda, Jaspal S. ; Foroni, Letizia ; Druker, Brian ; Guilhot, François ; Larson, Richard A. ; O'Brien, Stephen G. ; Rudoltz, Marc S. ; Mone, Manisha ; Wehrle, Elisabeth ; Modur, Vijay ; Goldman, John M. ; Radich, Jerald P. / Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia : An analysis from the International Randomized Study of Interferon and STI571 (IRIS). In: Blood. 2010 ; Vol. 116, No. 19. pp. 3758-3765.
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abstract = "This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases inBCR-ABL transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts > 10{\%} at 6 months and > 1{\%} at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) ≤ 0.1{\%}] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95{\%} EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3{\%} for patients in MMR at 18 months versus 26{\%} for patients with complete cytogenetic response but not MMR (P <.001). This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at www.clinicaltrials.gov as NCT00006343.",
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AU - Hughes, Timothy P.

AU - Hochhaus, Andreas

AU - Branford, Susan

AU - Müller, Martin C.

AU - Kaeda, Jaspal S.

AU - Foroni, Letizia

AU - Druker, Brian

AU - Guilhot, François

AU - Larson, Richard A.

AU - O'Brien, Stephen G.

AU - Rudoltz, Marc S.

AU - Mone, Manisha

AU - Wehrle, Elisabeth

AU - Modur, Vijay

AU - Goldman, John M.

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